Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic. Tag cloud generated 08 August, 2015 using data from PubMed, MeSH and CancerIndex
Mutated Genes and Abnormal Protein Expression (130)
Clicking on the Gene or Topic will take you to a separate more detailed page. Sort this list by clicking on a column heading e.g. 'Gene' or 'Topic'.
|TP53 ||17p13.1 ||P53, BCC7, LFS1, TRP53 || ||-TP53 and Esophageal Cancer || 350|
|EGFR ||7p12 ||ERBB, HER1, mENA, ERBB1, PIG61, NISBD2 ||Amplification |
|-EGFR Amplification in Esophageal Cancer || 103|
|ALDH2 ||12q24.2 ||ALDM, ALDHI, ALDH-E2 || ||-ALDH2 and Esophageal Cancer || 86|
|PTGS2 ||1q25.2-q25.3 ||COX2, COX-2, PHS-2, PGG/HS, PGHS-2, hCox-2, GRIPGHS ||Overexpression ||-PTGS2 (COX2) Overexpression in Esophageal Cancer |
-COX2 Polymorphisms and Esophageal Cancer
|MET ||7q31 ||HGFR, AUTS9, RCCP2, c-Met || ||-C-MET and Esophageal Cancer || 46|
|CDKN1A ||6p21.2 ||P21, CIP1, SDI1, WAF1, CAP20, CDKN1, MDA-6, p21CIP1 || ||-CDKN1A Expression in Esophageal Cancer || 41|
|CD9 ||12p13.3 ||MIC3, MRP-1, BTCC-1, DRAP-27, TSPAN29, TSPAN-29 || ||-CD9 expression in Esophageal Cancer || 39|
|ADH1B ||4q23 ||ADH2, HEL-S-117 || ||-ADH1B and Esophageal Cancer || 31|
|PIK3CA ||3q26.3 ||MCM, CWS5, MCAP, PI3K, CLOVE, MCMTC, p110-alpha ||Prognostic ||-PIK3CA and Esophogeal Cancer || 25|
|PLCE1 ||10q23 ||PLCE, PPLC, NPHS3 || ||-PLCE1 and Esophageal Cancer || 24|
|FGF4 ||11q13.3 ||HST, KFGF, HST-1, HSTF1, K-FGF, HBGF-4 || ||-FGF4 and Esophageal Cancer || 14|
|NOTCH1 ||9q34.3 ||hN1, AOS5, TAN1, AOVD1 || ||-NOTCH1 and Esophageal Cancer || 13|
|CTTN ||11q13 ||EMS1 ||Amplification |
|-CTTN and Esophogeal Cancer || 12|
|COL4A5 ||Xq22 ||ATS, ASLN, CA54 || ||-COL4A5 and Esophageal Cancer || 10|
|RB1 ||13q14.2 ||RB, pRb, OSRC, pp110, p105-Rb, PPP1R130 || ||-RB1 and Esophageal Cancer || 9|
|CYP2A6 ||19q13.2 ||CPA6, CYP2A, CYP2A3, P450PB, CYPIIA6, P450C2A || ||-CYP2A6 and Esophageal Cancer || 9|
|SOX2 ||3q26.3-q27 ||ANOP3, MCOPS3 || ||-SOX2 and Esoghogeal Cancer || 9|
|COL4A6 ||Xq22 ||DFNX6, DELXq22.3, CXDELq22.3 || ||-COL4A6 and Esophageal Cancer || 8|
|SPARC ||5q31.3-q32 ||ON || ||-SPARC and Esophageal Cancer || 8|
|CDC25B ||20p13 || || ||-CDC25B and Esophageal Cancer || 8|
|FSCN1 ||7p22 ||HSN, SNL, p55, FAN1 || ||-FSCN1 and Esophageal Cancer || 8|
|CRP ||1q23.2 ||PTX1 || ||-CRP and Esophageal Cancer || 8|
|ADH1C ||4q23 ||ADH3 || ||-ADH1C and Esophageal Cancer || 7|
|SPRR1A ||1q21-q22 ||SPRK || ||-SPRR1A and Esophageal Cancer || 7|
|NFE2L2 ||2q31 ||NRF2 || ||-NFE2L2 mutations in Esophageal Cancer || 7|
|C2orf40 ||2q12.2 ||ECRG4 || ||-C2orf40 and Esophageal Cancer || 7|
|SPRR2A ||1q21-q22 || || ||-SPRR2A and Esophageal Cancer || 7|
|CYR61 ||1p22.3 ||CCN1, GIG1, IGFBP10 || ||-CYR61 and Esophageal Cancer || 7|
|S100A9 ||1q21 ||MIF, NIF, P14, CAGB, CFAG, CGLB, L1AG, LIAG, MRP14, 60B8AG, MAC387 || ||-S100A9 and Esophageal Cancer || 6|
|STMN1 ||1p36.11 ||Lag, SMN, OP18, PP17, PP19, PR22, LAP18, C1orf215 || ||-STMN1 and Esophageal Cancer || 6|
|DEC1 ||9q32 ||CTS9 || ||-DEC1 and Esophageal Cancer || 6|
|SPRR2C ||1q21-q22 || || ||-SPRR2C and Esophageal Cancer || 6|
|SPRR2B ||1q21-q22 || || ||-SPRR2B and Esophageal Cancer || 6|
|SPRR1B ||1q21-q22 ||SPRR1, GADD33, CORNIFIN || ||-SPRR1B and Esophageal Cancer || 6|
|TNFRSF6B ||20q13.3 ||M68, TR6, DCR3, M68E, DJ583P15.1.1 || ||-TNFRSF6B and Esophageal Cancer || 5|
|EP300 ||22q13.2 ||p300, KAT3B, RSTS2 ||Prognostic ||-EP300 and Esophageal Cancer || 5|
|MMP7 ||11q22.2 ||MMP-7, MPSL1, PUMP-1 || ||-MMP7 Expression in Esophageal Cancer || 5|
|S100A8 ||1q21 ||P8, MIF, NIF, CAGA, CFAG, CGLA, L1Ag, MRP8, CP-10, MA387, 60B8AG || ||-S100A8 and Esophageal Cancer || 5|
|MIRLET7C ||21q21.1 ||LET7C, let-7c, MIRNLET7C, hsa-let-7c || ||-MicroRNA let-7c and Esophageal Cancer || 5|
|RRM2B ||8q23.1 ||P53R2, MTDPS8A, MTDPS8B || ||-RRM2B and Esophageal Cancer || 5|
|MMP11 ||22q11.23 ||ST3, SL-3, STMY3 || ||-MMP11 and Esophageal Cancer || 5|
|SKIL ||3q26 ||SNO, SnoA, SnoI, SnoN || ||-SKIL and Esophageal Cancer || 5|
|TMEFF2 ||2q32.3 ||TR, HPP1, TPEF, TR-2, TENB2, CT120.2 || ||-TMEFF2 and Esophageal Cancer || 5|
|HOTAIR ||12q13.13 ||HOXAS, HOXC-AS4, HOXC11-AS1, NCRNA00072 || ||-HOTAIR and Esophageal Cancer || 5|
|CTSB ||8p22 ||APPS, CPSB || ||-CTSB and Esophageal Cancer || 5|
|S100A2 ||1q21 ||CAN19, S100L || ||-S100A2 and Esophageal Cancer || 5|
|UCHL1 ||4p14 ||NDGOA, PARK5, PGP95, PGP9.5, Uch-L1, HEL-117, PGP 9.5 || ||-UCHL1 and Esophageal Cancer || 5|
|XRCC2 ||7q36.1 || || ||-XRCC2 and Esophageal Cancer || 4|
|PRINS ||10p12.1 ||NCRNA00074 || ||-PRINS and Esophageal Cancer || 4|
|BIRC2 ||11q22 ||API1, MIHB, HIAP2, RNF48, cIAP1, Hiap-2, c-IAP1 || ||-BIRC2 and Esophageal Cancer || 4|
|GPX3 ||5q33.1 ||GPx-P, GSHPx-3, GSHPx-P || ||-GPX3 and Esophageal Cancer || 4|
|TP53INP1 ||8q22 ||SIP, Teap, p53DINP1, TP53DINP1, TP53INP1A, TP53INP1B || ||-TP53INP1 and Esophageal Cancer || 4|
|PTTG1 ||5q35.1 ||EAP1, PTTG, HPTTG, TUTR1 || ||-PTTG1 and Esophageal Cancer || 4|
|LCN2 ||9q34 ||24p3, MSFI, NGAL || ||-LCN2 and Esophageal Cancer || 4|
|HOXA13 ||7p15.2 ||HOX1, HOX1J || ||-HOXA13 and Esophageal Cancer || 4|
|RHBDF2 ||17q25.1 ||TEC, TOC, TOCG, RHBDL5, RHBDL6, iRhom2 ||Germline ||-RHBDF2 mutations in Tylosis - a familial esophageal cancer syndrome || 4|
|PTPN1 ||20q13.1-q13.2 ||PTP1B || ||-PTPN1 and Esophageal Cancer || 4|
|KDM4C ||9p24.1 ||GASC1, JHDM3C, JMJD2C, TDRD14C || ||-KDM4C and Esophageal Cancer || 3|
|CTSL ||9q21.33 ||MEP, CATL, CTSL1 || ||-CTSL1 and Esophageal Cancer || 3|
|ELF3 ||1q32.2 ||ERT, ESX, EPR-1, ESE-1 || ||-ELF3 and Esophageal Cancer || 3|
|SOX17 ||8q11.23 ||VUR3 || ||-SOX17 and Esophageal Cancer || 3|
|DMBT1 ||10q26.13 ||GP340, muclin || ||-DMBT1 supression in Esophageal Cancer? || 3|
|LOXL2 ||8p21.3 ||LOR2, WS9-14 || ||-LOXL2 and Esophageal Cancer || 3|
|MAPK14 ||6p21.3-p21.2 ||RK, p38, CSBP, EXIP, Mxi2, CSBP1, CSBP2, CSPB1, PRKM14, PRKM15, SAPK2A, p38ALPHA || ||-MAPK14 and Esophageal Cancer || 3|
|PLA2G4A ||1q25 ||PLA2G4, cPLA2-alpha || ||-PLA2G4A and Esophageal Cancer || 3|
|TOP2A ||17q21-q22 ||TOP2, TP2A || ||-TOP2A Expression in Esophageal Cancer || 3|
|CKS2 ||9q22 ||CKSHS2 || ||-CKS2 and Esophageal Cancer || 3|
|KMT2D ||12q13.12 ||ALR, KMS, MLL2, MLL4, AAD10, KABUK1, TNRC21, CAGL114 || ||-KMT2D and Esophageal Cancer || 3|
|ANO1 ||11q13.3 ||DOG1, TAOS2, ORAOV2, TMEM16A || ||-ANO1 and Esophageal Cancer || 3|
|KRT7 ||12q13.13 ||K7, CK7, SCL, K2C7 || ||-KRT7 and Esophageal Cancer || 3|
|MT1G ||16q13 ||MT1, MT1K || ||-MT1G and Esophageal Cancer || 3|
|ODC1 ||2p25 ||ODC || ||-ODC1 and Esogapheal Cancer || 3|
|NQO2 ||6p25.2 ||QR2, DHQV, DIA6, NMOR2 || ||-NQO2 and Esophageal Cancer || 3|
|CREBBP ||16p13.3 ||CBP, RSTS, KAT3A ||GWS ||-CREBBP and Esophageal Cancer || 3|
|FGF19 ||11q13.1 || || ||-FGF19 and Esophageal Cancer || 3|
|PERP ||6q24 ||THW, KCP1, PIGPC1, KRTCAP1, dJ496H19.1 || ||-PERP and Esophageal Cancer || 3|
|CLDN3 ||7q11.23 ||RVP1, HRVP1, C7orf1, CPE-R2, CPETR2 || ||-CLDN3 and Esophageal Cancer || 3|
|IRF2 ||4q34.1-q35.1 ||IRF-2 || ||-IRF2 and Esophageal Cancer || 2|
|POLK ||5q13 ||DINP, POLQ, DINB1 || ||-POLK and Esophageal Cancer || 2|
|FAT1 ||4q35 ||FAT, ME5, CDHF7, CDHR8, hFat1 || ||-FAT1 mutation in Esophogeal Cancer || 2|
|AKR1C2 ||10p15-p14 ||DD, DD2, TDD, BABP, DD-2, DDH2, HBAB, HAKRD, MCDR2, SRXY8, DD/BABP, AKR1C-pseudo || ||-AKR1C2 and Esophageal Cancer || 2|
|GPX2 ||14q24.1 ||GPRP, GPx-2, GI-GPx, GPRP-2, GPx-GI, GSHPx-2, GSHPX-GI || ||-GPX2 and Esophageal Cancer || 2|
|SOX6 ||11p15.3 ||SOXD, HSSOX6 || ||-SOX6 and Esophageal Cancer || 2|
|PTK7 ||6p21.1-p12.2 ||CCK4, CCK-4 || ||-PTK7 and Esophageal Cancer || 2|
|PRDX1 ||1p34.1 ||PAG, PAGA, PAGB, PRX1, PRXI, MSP23, NKEFA, TDPX2, NKEF-A || ||-PRDX1 and Esophageal Cancer || 2|
|RARRES1 ||3q25.32 ||LXNL, TIG1, PERG-1 || ||-RARRES1 and Esophageal Cancer || 2|
|AQP3 ||9p13 ||GIL, AQP-3 || ||-AQP3 and Esophageal Cancer || 2|
|S100A10 ||1q21 ||42C, P11, p10, GP11, ANX2L, CAL1L, CLP11, Ca, ANX2LG || ||-S100A10 and Esophageal Cancer || 2|
|IL23R ||1p31.3 || || ||-IL23R and Esophageal Cancer || 2|
|SERPINA1 ||14q32.1 ||PI, A1A, AAT, PI1, A1AT, PRO2275, alpha1AT || ||-SERPINA1 and Esophageal Cancer || 2|
|DGCR8 ||22q11.2 ||Gy1, pasha, DGCRK6, C22orf12 || ||-DGCR8 and Esophageal Cancer || 2|
|REG1A ||2p12 ||P19, PSP, PTP, REG, ICRF, PSPS, PSPS1 || ||-REG1A and Esophageal Cancer || 2|
|ADAMTS9 ||3p14.1 || || ||-ADAMTS9 and Esophageal Cancer || 2|
|HLA-E ||6p21.3 ||MHC, QA1, EA1.2, EA2.1, HLA-6.2 || ||-HLA-E and Esophageal Cancer || 2|
|DRD2 ||11q23 ||D2R, D2DR || ||-DRD2 and Esophageal Cancer || 2|
|CD47 ||3q13.1-q13.2 ||IAP, OA3, MER6 || ||-CD47 and Esophageal Cancer || 2|
|IFITM1 ||11p15.5 ||9-27, CD225, IFI17, LEU13, DSPA2a || ||-IFITM1 and Esophageal Cancer || 2|
|GATA5 ||20q13.33 ||GATAS, bB379O24.1 || ||-GATA5 and Esophageal Cancer || 2|
|HHIP ||4q28-q32 ||HIP || ||-HHIP and Esophageal Cancer || 2|
|RAC3 ||17q25.3 || || ||-RAC3 and Esophageal Cancer || 2|
|ITGA6 ||2q31.1 ||CD49f, VLA-6, ITGA6B || ||-ITGA6 and Esophageal Cancer || 2|
|PINX1 ||8p23 ||LPTL, LPTS || ||-PINX1 and Esophageal Cancer || 2|
|KMT2C ||7q36.1 ||HALR, MLL3 || ||-KMT2C and Esophageal Cancer || 2|
|CDH3 ||16q22.1 ||CDHP, HJMD, PCAD || ||-CDH3 and Esophageal Cancer || 2|
|RASSF10 ||11p15.2 || || ||-RASSF10 and Esophageal Cancer || 1|
|PDE4DIP ||1q12 ||MMGL, CMYA2 || ||-PDE4DIP and Esophageal Cancer || 1|
|FEZ1 ||11q24.2 || || ||-FEZ1 and Esophageal Cancer || 1|
|NEURL1 ||10q25.1 ||neu, NEUR1, NEURL, RNF67, neu-1, bA416N2.1 || ||-NEURL and Esophageal Cancer || 1|
|PLCD1 ||3p22-p21.3 ||NDNC3, PLC-III || ||-PLCD1 and Esophageal Cancer || 1|
|NEMF ||14q22 ||NY-CO-1, SDCCAG1 || ||-NEMF and Esophageal Cancer || 1|
|COX6C ||8q22.2 || || ||-COX6C and Esophageal Cancer || 1|
|CSTB ||21q22.3 ||PME, ULD, CST6, EPM1, STFB, EPM1A || ||-CSTB and Esophageal Cancer || 1|
|FAT2 ||5q33.1 ||CDHF8, CDHR9, HFAT2, MEGF1 || ||-FAT2 mutation in Esophogeal Cancer || 1|
|SEPT5 ||22q11.21 ||H5, CDCREL, PNUTL1, CDCREL1, CDCREL-1, HCDCREL-1 || ||-SEPT5 and Esophageal Cancer || 1|
|PRRX1 ||1q24 ||PMX1, PRX1, AGOTC, PHOX1, PRX-1 || ||-PRRX1 and Esophageal Cancer || 1|
|SETD1B ||12q24.31 ||KMT2G, Set1B ||GWS ||-SETD1B and Esophageal Cancer || 1|
|COPS6 ||7q22.1 ||CSN6, MOV34-34KD || ||-COPS6 and Esophageal Cancer || 1|
|FTL ||19q13.33 ||LFTD, NBIA3 || ||-FTL and Esophageal Cancer || 1|
|FNBP1 ||9q34 ||FBP17 || ||-FNBP1 and Esophageal Cancer || 1|
|SEPP1 ||5q31 ||SeP, SELP, SEPP || ||-SEPP1 and Esophageal Cancer || 1|
|ZNF750 ||17q25.3 ||ZFP750 ||Deletion ||-ZNF750 mutation in Esophageal Cancer || 1|
|TNFRSF14 ||1p36.32 ||TR2, ATAR, HVEA, HVEM, CD270, LIGHTR || ||-TNFRSF14 and Esophageal Cancer || 1|
|PDGFRL ||8p22-p21.3 ||PDGRL, PRLTS || ||-PDGFRL and Esophageal Cancer || 1|
|ASH1L ||1q22 ||ASH1, KMT2H, ASH1L1 || ||-ASH1L and Esophageal Cancer || 1|
|GJB2 ||13q11-q12 ||HID, KID, PPK, CX26, DFNA3, DFNB1, NSRD1, DFNA3A, DFNB1A || ||-GJB2 and Esophageal Cancer || 1|
|TPM4 ||19p13.1 ||HEL-S-108 || ||-TPM4 and Esophageal Cancer || 1|
|MAFG ||17q25.3 ||hMAF || ||-MAFG and Esophageal Cancer || 1|
|ADAM29 ||4q34 ||CT73, svph1 || ||-ADAM29 mutations in Esophageal Cancer || 1|
|S100A3 ||1q21 ||S100E || ||-S100A3 and Esophageal Cancer || 1|
|MIR1256 ||1 ||MIRN1256, hsa-mir-1256 || ||-MicroRNA miR-1256 and Esophageal Cancer || 1|
Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).
Peng XE, Chen HF, Hu ZJ, Shi XSIndependent and combined effects of environmental factors and CYP2C19 polymorphisms on the risk of esophageal squamous cell carcinoma in Fujian Province of China.
BMC Med Genet. 2015; 16:15 [PubMed
] Free Access to Full Article Related Publications
BACKGROUND: The purpose of this study was to explore the effects of CYP2C19 gene polymorphisms and various environmental factors and their interactions on the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population.
METHODS: A 1:2 frequency-matched case control study of 285 patients and 570 controls was conducted from June 2010 to May 2011 in AnXi of Fujian province, China. Environmental factors were investigated using a self-administered questionnaire and genotypes were determined using polymerase chain reaction restriction fragment length polymorphism based methods. Unconditional logistic regression models were used for statistical evaluation.
RESULTS: Current or former smoking, consumption of pickled vegetables or hot beverages/food, having a first degree relative with ESCC and history of reflux esophagitis were significantly associated with increased ESCC risk, whereas tea drinking and consumption of fresh vegetables and fruits were significantly associated with decreased risk. The CYP2C19*2 GA/AA genotype was significantly more prevalent in ESCC patients and individuals with at least one copy of the CYP2C19*2 A allele had a 3.19-fold increased risk (adjusted 95% confidence interval (CI): 2.21-4.61, P < 0.001) of ESCC compared with those without this allele. We found no significant associations between CYP2C19*3 genotypes and ESCC. The Cyp2C19*2 polymorphism appeared to have a multiplicative joint effect with tea drinking and hot beverage/food consumption (gene-tea drinking: P(interaction) = 0.042; hot beverage/food consumption: P(interaction) = 6.98 × 10(-6)) and an additive joint effect with pickled vegetable consumption (interaction contrast ratio = 1.96, 95% CI: 0.12-3.80).
CONCLUSIONS: Our findings suggest that the CYP2C19*2 polymorphism plays an important role in the development of ESCC in the Chinese population, modified by tea drinking and consumption of pickled vegetables or hot beverages/food. Further studies are warranted to confirm our results.
Zhang X, Xu Y, He C, et al.Elevated expression of CCAT2 is associated with poor prognosis in esophageal squamous cell carcinoma.
J Surg Oncol. 2015; 111(7):834-9 [PubMed
] Related Publications
BACKGROUND AND OBJECTIVES: CCAT2, a novel long non-coding RNAs (lncRNAs), is found to promote the metastasis and invasion of colon, lung, and breast cancers. This study aimed to investigate the level of CCAT2 in esophageal squamous cell carcinoma (ESCC) and to elucidate its clinical significance.
METHODS: The expression level of CCAT2 and the status of MYC amplification were examined in 229 ESCC samples using quantitative real- time PCR.
RESULTS: CCAT2 was upregulated in ESCC tissues, especially in cases with lymph node metastasis (LNM), advanced TNM stages, and MYC amplification. Furthermore, the level of CCAT2 was positively correlated with TNM stages, LNM, and the number of positive lymph nodes. High CCAT2 expression and MYC amplification were significantly associated with TNM stages and LNM. Survival analyses revealed that high CCAT2 expression and MYC amplification were significantly associated with poorer overall survival in ESCC patients. Furthermore, patients with high CCAT2 expression and MYC amplification had a 2.199-fold increased risk of death compared with those with low CCAT2 expression and MYC non-amplification.
CONCLUSIONS: Our study provides the first evidence associating CCAT2 expression and poor survival in ESCC. CCAT2 may be a prognostic biomarker and therapeutic target for ESCC.
Cancers of the stomach and esophagus are among the most challenging cancers of the GI tract to treat, associated with poor median survivals for metastatic disease and significant, sometimes prolonged, deteriorations in patient performance status as the diseases progress. However, in the past decade, we have begun to better understand disease biology and carcinogenesis, leading to the identification of subtypes of these diseases. There is also an increasing awareness of the global heterogeneity of disease and its impact on drug development. Our improved understanding of the molecular underpinnings of gastric and esophageal cancers has been accompanied with the development of novel therapeutic strategies. Recent actively investigated targets in this disease include human epidermal growth factor receptor 2, angiogenesis, MET, and immune checkpoint inhibition, with approvals of two new targeted agents, trastuzumab and ramucirumab. Improvements in our ability to deliver cytotoxic therapy, which is better tolerated and allows patients an opportunity to benefit from second- and more advanced lines of therapy, have also been observed. In this review, the current state-of-the-art management of advanced and metastatic gastric and esophageal adenocarcinomas, specifically highlighting the development of targeted therapies in these diseases, is described.
Chunli W, Jiajie H, Lifei W, et al.[IGHMBP2 overexpression promotes cell migration and invasion in esophageal squamous carcinoma].
Yi Chuan. 2015; 37(4):360-6 [PubMed
] Related Publications
Immunoglobulin mu binding protein 2 (IGHMBP2) is located in 11q13.2, which is frequently amplified in esophageal squamous cell carcinoma (ESCC). IGHMBP2 encodes a helicase involved in DNA replication and repair. IGHMBP2 protein also regulates gene transcription. The present study aims to explore the amplification of IGHMBP2 and its potential role in ESCC. A further analysis of our previously reported array-CGH data showed that IGHMBP2 was amplified in 28.9% of primary ESCC tumors. Fluorescence in situ hybridization (FISH) and Western blot showed that IGHMBP2 was amplified and overexpressed in KYSE30, KYSE180, KYSE510 and KYSE150 esophageal cancer cell lines. Transwell assays demonstrated that knockdown of IGHMBP2 in KYSE30 and KYSE150 inhibited cell invasion and migration, and increased the expression levels of E-cadherin. When rescue plasmids expressing IGHMBP2 were introduced, the abilities of cell invasion and migration were restored. These data suggest that IGHMBP2 overexpression may promote invasion and migration of ESCC cells through down-regulation of E-cadherin.
Yingying L, Zhiguang L, Li W, et al.[Serum miRNAs as new biomarkers for esophageal squamous cell carcinoma].
Yi Chuan. 2015; 37(4):315-20 [PubMed
] Related Publications
Esophageal squamous cell carcinoma (ESCC) is one of the most common types of malignancies in China. Most ESCC patients are diagnosed at middle to late stages with poor prognosis due to the lack of an effective method for early diagnosis. MicroRNAs (miRNAs) are a family of endogenous small non-coding RNAs that can regulate ESCC development and progression by repressing their specific target genes' expression. Compared to traditional biomarkers (e.g., mRNAs and proteins), miRNAs are more stable and can be readily screened and accurately quantitated and analyzed, making them ideal new-generation of biomarkers for early cancer detection and prognostic evaluation. Recent studies have shown that the changes of the expression levels of some serum miRNAs from ESCC patients significantly correlate with their diagnostic and prognostic outcome. In this review, we summarize the trend of the expression changes of miRNAs in ESCC patients' serum and discuss the possibility of detecting these miRNAs' expression changes as a novel method for ESCC early diagnosis and prognostic evaluation. Notably, the results of serum miRNAs from different detection methods are not completely consistent. Thus, we also discuss several possible reasons for such inconsistency.
BACKGROUND: Biomarkers are needed to improve current diagnosis and surveillance strategies for patients with Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). Macrophage inhibitory cytokine 1/growth differentiation factor 15 (MIC-1/GDF15) tissue and plasma levels have been shown to predict disease progression in other cancer types and was therefore evaluated in BO/OAC.
METHODS: One hundred thirty-eight patients were studied: 45 normal oesophagus (NE), 37 BO, 16 BO with low-grade dysplasia (LGD) and 40 OAC.
RESULTS: Median tissue expression of MIC-1/GDF15 mRNA was ⩾25-fold higher in BO and LGD compared to NE (P<0.001); two-fold higher in OAC vs BO (P=0.039); and 47-fold higher in OAC vs NE (P<0.001). Relative MIC-1/GDF15 tissue expression >720 discriminated between the presence of either OAC or LGD vs NE with 94% sensitivity and 71% specificity (ROC AUC 0.86, 95% CI 0.73-0.96; P<0.001). Macrophage inhibitory cytokine 1/growth differentiation factor 15 plasma values were also elevated in patients with OAC vs NE (P<0.001) or BO (P=0.015).High MIC-1/GDF15 plasma levels (⩾1140 pg ml(-1)) were an independent predictor of poor survival for patients with OAC (HR 3.87, 95% CI 1.01-14.75; P=0.047).
CONCLUSIONS: Plasma and tissue levels of MIC-1/GDF15 are significantly elevated in patients with BO, LGD and OAC. Plasma MIC-1/GDF15 may have value in diagnosis and monitoring of Barrett's disease.
Chen J, Lan T, Zhang W, et al.Dasatinib enhances cisplatin sensitivity in human esophageal squamous cell carcinoma (ESCC) cells via suppression of PI3K/AKT and Stat3 pathways.
Arch Biochem Biophys. 2015; 575:38-45 [PubMed
] Related Publications
The clinical efficacy of cisplatin in esophageal squamous cell carcinoma (ESCC) treatment remains undesirable. Src, a non-receptor tyrosine kinase involved in multiple fields of tumorigenesis, recently has been indicated as a promising therapeutic target in the treatment of solid tumors including ESCC. However, whether inhibition of Src activity can increase cisplatin efficacy in ESCC cells remains unknown. The present study found that inhibition of Src by its inhibitor-dasatinib sensitized ESCC cells to cisplatin in vitro. Our data also suggest a likely mechanism for this synergy that dasatinib reduces expression of critical oncogenic members of the signaling pathways, such as AKT or Stat3, and cisplatin-resistant molecules, such as ERCC1 and BRCA1, under the control of Src. Furthermore, dasatinib could sensitize ESCC cells to another platin-based agent, carboplatin. Therefore, this study provides a potential target for improving cisplatin efficacy in ESCC therapy.
Xu Y, He J, Wang Y, et al.miR-889 promotes proliferation of esophageal squamous cell carcinomas through DAB2IP.
FEBS Lett. 2015; 589(10):1127-35 [PubMed
] Related Publications
MicroRNAs have been reported to play critical roles in various cancers, but there has been no study on the role of miR-889 in cancers. Here, we report that over-expression of miR-889 leads to rapid proliferation of EC109 and EC9706 cells in vitro and in vivo by inducing cells into S-phase. Using bioinformatics methods, DAB2IP was further confirmed to be a direct target of miR-889. In addition, the expression of DAB2IP, which was negatively correlated with that of miR-889, was significantly associated with clinicopathological features of ESCC patients. In conclusion, miR-889 is an important regulator in ESCC and both miR-889 and DAB2IP may serve as promising biomarkers and therapeutic targets in patients with ESCC.
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets.
Song Y, Wang Y, Xu L, et al.A genetic variant in CHRNB3-CHRNA6 increases risk of esophageal squamous cell carcinoma in Chinese populations.
Carcinogenesis. 2015; 36(5):538-42 [PubMed
] Related Publications
Nicotinic acetylcholine receptors are important regulators of smoking behavior and tobacco carcinogenesis. We studied the association of the CHRNB3-A6 variant rs13280604 in relation to esophageal squamous cell carcinoma (ESCC) in Chinese populations. Two independent case-control studies were conducted. The first case-control study, consisted of 866 ESCC patients and 1621 healthy controls from Northern China, and the second case-control study consisted of 853 ESCC patients and 860 unrelated controls from Southern China. A logistic regression model was used to evaluate the associations of rs13280604 with cancer risk. We found that Rs13280604 GG/AG genotypes were significantly associated with increased risk for ESCC in both case-control studies from Northern [odds ratio (OR), 1.42, 95% confidence interval (CI), 1.19-1.70, P = 1.1×10(-4)], Southern China (OR, 1.56, 95% CI, 1.26-1.93, P = 5.2×10(-5)), and the combined population of both studies (OR, 1.44, 95% CI, 1.26-1.65, P = 8.7×10(-8)), respectively. Our results suggest that this CHRNB3-A6 variant confers susceptibility to ESCC risk. However, future larger studies are needed to validate our finding.
Slaby O, Srovnal J, Radova L, et al.Dynamic changes in microRNA expression profiles reflect progression of Barrett's esophagus to esophageal adenocarcinoma.
Carcinogenesis. 2015; 36(5):521-7 [PubMed
] Related Publications
Esophageal adenocarcinoma (EAC) is highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. MicroRNAs (miRNAs) are small, non-coding RNAs that function as posttranscriptional regulators of gene expression and were repeatedly proved to play key roles in pathogenesis of BE as well as EAC. In our study, we used Affymetrix GeneChip miRNA arrays to obtain miRNA expression profiles in total of 119 tissue samples [24 normal esophageal mucosa (EM), 60 BE and 35 EAC]. We identified a number of miRNAs, that showed altered expression progressively in sequence EM, BE and EAC, including for instance miR-21, miR-25, miR-194 and miR-196a with increasing levels (P < 0.0015) and miR-203, miR-205, miR-210 and miR-378 with decreasing levels (P < 0.0001). The subsequent analysis revealed four diagnostic miRNA signatures enabling to distinguish EM and BE [12 miRNAs, area under curve (AUC) = 0.971], EM and EAC (13 miRNAs, AUC = 1.0), BE without and BE with dysplasia (21 miRNAs, AUC = 0.856) and BE without dysplastic changes and BE with dysplasia together with EAC (2 miRNAs, AUC = 0.886). We suggest that miRNA expression profiling expands current knowledge in molecular pathology of Barrett's-based carcinogenesis and enables identification of molecular biomarkers for early detection of BE dysplasia and progression to EAC.
Ozawa Y, Nakamura Y, Fujishima F, et al.Decreased expression of ARID1A contributes to infiltrative growth of esophageal squamous cell carcinoma.
Tohoku J Exp Med. 2015; 235(3):185-91 [PubMed
] Related Publications
The clinical outcome for esophageal squamous cell carcinoma (ESCC) patients is often poor because of the invasive nature of this tumor type. AT-rich interactive domain 1A (ARID1A) functions as a tumor suppressor, and its gene mutation has been reported in various human malignancies. ARID1A is a non-catalytic subunit of the SWItch/Sucrose Non Fermentable (SWI/SNF) chromatin-remodeling complex that regulates gene transcription. Decreased expression of ARID1A protein has been reported to decrease the expression of E-cadherin, an adhesion protein. However, the correlation between ARID1A and E-cadherin expression status in ESCC remains largely unknown. To address this issue, we examined the expression of ARID1A and E-cadherin in tumor specimens excised from 83 ESCC patients using immunohistochemical analysis. The intensity of the ARID1A immunoreactivity was significantly lower in tumors with a growth pattern characterized by ill-defined borders than that in tumors with an expansive growth pattern having a well-demarcated border or tumors with an intermediate growth pattern. Thus, decreased ARID1A immunoreactivity correlated with infiltrative growth of ESCC. In contrast, E-cadherin status did not correlate with the infiltrative growth pattern of ESCC. Moreover, ARID1A expression status did not significantly correlate with any of other clinicopathological factors, E-cadherin expression levels, or the clinical outcome of the patients. On the other hand, the patients with tumors expressing low levels of E-cadherin exhibited significantly lower survival rates than those with high expression. In conclusion, reduced ARID1A expression in tumor tissues contributes to infiltrative growth of ESCC, irrespective of E-cadherin expression levels.
Ide S, Toiyama Y, Shimura T, et al.MicroRNA-503 promotes tumor progression and acts as a novel biomarker for prognosis in oesophageal cancer.
Anticancer Res. 2015; 35(3):1447-51 [PubMed
] Related Publications
AIM: This study investigated microRNA (miR)-503 expression levels and evaluated its clinical significance in patients with oesophageal cancer (EC).
MATERIALS AND METHODS: miR-503 expression was quantified by quantitative reverse transcription-polymerase chain reaction in 49 EC tissue samples and 12 adjacent normal tissues from 49 patients with EC. The association between miR-503 expression and clinicopathological factors, including prognostic outcomes, were assessed.
RESULTS: miR-503 was found up-regulated in EC tissues compared to adjacent normal tissues. High miR-503 expression was significantly associated with large tumor size. Kaplan-Meier analysis showed that patients with high miR-503 expression had significantly poorer disease-free and overall survival than those with lower expression levels. High miR-503 expression was identified as an independent prognostic predictor in patients with EC according to multivariate analysis.
CONCLUSION: miR-503 expression affects tumor cell proliferation in EC. Evaluation of miR-503 expression might thus help identify patients with EC with poor prognosis and higher risk of early recurrence.
Guo XF, Wang J, Lei XF, et al.XPD Lys751Gln polymorphisms and the risk of esophageal cancer: an updated meta-analysis.
Intern Med. 2015; 54(3):251-9 [PubMed
] Related Publications
OBJECTIVE: Published data regarding the association between xeroderma pigmentosum group D XPD Lys751Gln polymorphisms and esophageal cancer (EC) cancer remain controversial. The present meta-analysis aimed to obtain a more precise estimation of the relationship between XPD Lys751Gln polymorphisms and the risk of EC.
METHODS: All eligible case-control studies of Lys751Gln polymorphisms and susceptibility to EC were selected from PubMed, Web of Science and CNKI up to October 2013. The data were extracted, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.
RESULTS: A total of 21 case-control studies from 19 reports were assessed in this meta-analysis, including 6,581 cases and 8,251 controls. There was a significant association between the XPD Lys751Gln polymorphism and the risk of esophageal cancer in the overall population (Dominant model: OR=1.30, 95%CI: 1.07-1.57, p<0.05; Lys/Gln vs. Gln/Gln: OR=1.20, 95%CI: 1.05-137, p<0.05; Gln/Gln vs. Lys/Lys: OR=1.76, 95%CI: 1.08-2.85, p=0.02; Recessive model: OR=1.48, 95%CI: 1.06-2.07, p=0.02). Similar results were found when stratified according to the cancer type, ethnicity and control source. However, no associations were found among smokers or drinkers.
CONCLUSION: The results of this meta-analysis suggest that XPD Lys751Gln polymorphisms contribute to susceptibility to EC.
Zeki S, Fitzgerald RCThe use of molecular markers in predicting dysplasia and guiding treatment.
Best Pract Res Clin Gastroenterol. 2015; 29(1):113-24 [PubMed
] Related Publications
The ability to stratify patients based on the risk of progression to oesophageal adenocarcinoma would provide benefit to patients as well as deliver a more cost effective surveillance programme. Current practice is to survey all patients with Barrett's oesophagus (BO) and use histological diagnoses to guide further management. However, reliance on histology alone has its drawbacks. We are currently unable to reliably stratify the risk of progression of patients with non-dysplastic BO based on any particular histological feature. There is also considerable variability in histological interpretation. An obvious recourse has been to rely on identifying molecular features possibly as an adjunct to histology, to better diagnose and stratify patients. To this end, p53 immunohistochemistry can be used as a useful adjunct to risk stratify and clarify histological grades, particularly low-grade dysplasia. Other markers of progression, although not yet in a clinically applicable format, are promising. Measurements of promoter methylation and also genomic instability such as loss of heterozygosity and copy number alterations show promise especially as high throughput genetic technologies reach maturity. The enduring hope is that these molecular biomarkers will make the transition to clinical applicability either in the direct endoscopic setting or even using non-endoscopic methods.
Shi WH, Wu QQ, Li SQ, et al.Upregulation of the long noncoding RNA PCAT-1 correlates with advanced clinical stage and poor prognosis in esophageal squamous carcinoma.
Tumour Biol. 2015; 36(4):2501-7 [PubMed
] Related Publications
Recent studies reveal that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. Prostate cancer-associated ncRNA transcript 1 (PCAT-1) is one of the lncRNAs involved in cell apoptosis and proliferation of prostate cancer. This study aimed to assess the potential role of PCAT-1 specifically in the pathogenesis of esophageal squamous cell carcinoma (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PCAT-1 in matched cancerous tissues and adjacent noncancerous tissues from 130 patients with ESCC, 34 patients with non-small cell lung cancer (NSCLC), and 30 patients with gastric carcinoma (GC). The correlation of PCAT-1 with clinicopathological features and prognosis were also analyzed. The expression of PCAT-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (70.8%, p < 0.01), and the high level of PCAT-1 expression was significantly correlated with invasion of the tumor (p = 0.024), advanced clinical stage (p = 0.003), lymph node metastasis (p = 0.032), and poor prognosis. However, PCAT-1 mRNA expression had no significant difference between paired primary cancerous tissues and the adjacent noncancerous tissues in 34 cases of NSCLC (p = 0.293) and 30 cases of GC (p = 0.125). High expression of PCAT-1 was specifically correlated with invasion of cancer tissues, metastasis of lymph node, and advanced tumor stage of ESCC. High expression of PCAT-1 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Adjuvant therapy targeting PCAT-1 molecule might be effective in treatment of ESCC.
Yan YL, Chen X, Liang HJ, et al.Lack of association between EPHX1 polymorphism and esophageal cancer risk: evidence from meta-analysis.
Dis Esophagus. 2015 Feb-Mar; 28(2):164-71 [PubMed
] Related Publications
The microsomal epoxide hydrolase 1 (EPHX1) Tyr113His and His139Arg polymorphisms have been reported to be associated with esophageal cancer (EC) risk, yet the results of these previous results have been inconsistent or controversial. The objective of this study was to explore whether the EPHX1 Tyr113His and His139Arg polymorphisms confer risk to EC. The relevant studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database until May 2013. The association between the EPHX1 Tyr113His and His139Arg polymorphisms and EC risk was pooled by odds ratios (ORs) together with their 95% confidence intervals (95%CIs). A total of eight case-control studies with 1163 EC patients and 1868 controls (seven studies for both Tyr113His and His139Arg polymorphisms, one study only for Tyr113His polymorphism) were eventually identified. We found no association between EPHX1 Tyr113His and His139Arg polymorphisms and EC risk in overall population (For Tyr113His: His vs. Tyr: OR = 1.05, 95%CI = 0.95-1.15, P = 0.379; His/His vs. Tyr/Tyr: OR = 1.04, 95%CI = 0.88-1.22, P = 0.208; His/Tyr vs. Tyr/Tyr: OR = 0.96, 95%CI = 0.80-1.15, P = 0.577; His/His vs. His/Tyr + Tyr/Tyr: OR = 1.10, 95%CI = 0.96-1.26, P = 0.164; His/His + His/Tyr vs. Tyr/Tyr: OR = 1.01, 95%CI = 0.90-1.12, P = 0.543. For His139Arg: Arg vs. His: OR = 1.04, 95%CI = 0.94-1.14, P = 0.465; Arg/Arg vs. His/His: OR = 1.06, 95%CI = 0.91-1.24, P = 0.470; Arg/His vs. His/His: OR = 1.03, 95%CI = 0.91-1.16, P = 0.673; Arg/Arg vs. Arg/His + His/His: OR = 1.04, 95%CI = 0.85-1.27, P = 0.708; Arg/Arg + Arg/His vs. His/His: OR = 1.02, 95%CI = 0.93-1.13, P = 0.617). In subgroup analysis based on ethnicity, significant association has been found in neither EPHX1 Tyr113His nor His139Arg polymorphism. The current meta-analysis suggests no evidence of association between the EPHX1 polymorphism and EC risk.
Li K, Yin X, Yang H, et al.Association of the genetic polymorphisms in XRCC6 and XRCC5 with the risk of ESCC in a high-incidence region of North China.
Tumori. 2015 Jan-Feb; 101(1):24-9 [PubMed
] Related Publications
BACKGROUND: The XRCC6 and XRCC5 genes are part of the nonhomologous end-joining (NHEJ) pathway, which is the main mechanism repairing DNA double-strand breaks (DSBs) in human cells. Genetic variations of XRCC6 and XRCC5 might contribute to esophageal squamous cell carcinoma (ESCC) susceptibility.
METHODS: ESCC patients (n = 189) and cancer-free controls (n = 189) were recruited in an ESCC high-risk area of north China. Then the rs2267437 (XRCC6), rs3835 (XRCC5) and rs16855458 (XRCC5) polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.
RESULTS: A significant difference in genotype distribution and allele frequency of rs2267437 (XRCC6) was observed between the cases and controls. The CG carriers were at higher risk of ESCC (p = 0.001, odds ratio [OR] = 2.040, 95% confidence interval [95% CI], 1.323-3.147). G allele carriers were also associated with an increased ESCC risk (p = 0.003, OR = 1.868, 95% CI, 1.230-2.836). In the 2 polymorphisms of XRCC5, no significant difference was found between both groups in the distribution of either genotype or allelic frequency. But in the haplotypes established by the single nucleotide polymorphisms (SNPs) of XRCC5, the haplotype AT and CC separately increased by 4.28- and 2.31-fold the risk ratio of ESCC (p = 0.01, OR = 4.28, 95% CI, 1.40-13.05; p = 0.03, OR = 2.31, 95% CI, 1.11-4.80, respectively). In addition, gene-smoking or gene-drinking interactions, and their effect on the risk of ESCC were observed, but no significant gene-environment interaction was demonstrated.
CONCLUSIONS: In conclusion, both the CG carriers/G allele carriers of rs2267437 (XRCC6) and the haplotype AT/CC established by the SNPs of XRCC5 are associated with ESCC susceptibility.
Stánitz É, Juhász K, Gombos K, et al.Alteration of miRNA expression correlates with lifestyle, social and environmental determinants in esophageal carcinoma.
Anticancer Res. 2015; 35(2):1091-7 [PubMed
] Related Publications
BACKGROUND/AIM: Esophageal cancer (EC) is the eighth most common cancer with a highly aggressive potency. Considering the poor survival of esophageal carcinoma there is a need for useful molecular biomarkers for prevention and early detection. Our aim was to determine the significance of altered microRNA (miRNA) expression in esophageal cancer, in relation to lifestyle, social and environmental factors.
MATERIALS AND METHODS: The relative expression levels of the following miRNAs: miR-21, miR-143, miR-196a, miR-203, miR-205 and miR-221 were monitored in control and esophageal squamous-cell carcinoma (ESCC) samples using real-time polymerase chain reaction (RT-PCR). miRNA expression pattern of tumor tissues were evaluated according to patients' social status, living condition, smoking and drinking habits alone and in combinations.
RESULTS: miR-21, miR-143, miR-203, miR-205 and miR-221 were over-expressed in esophageal cancer compared with normal tissues. Increased expression of miR-205 was related to smoking, while excessive alcohol consumption showed a correlation with under-expression of miR-143, miR-203 and miR-205 in tumor samples. Significant associations were detected between reduced expression of miR-143, miR-203 and low social status, and combination of smoking and heavy drinking.
CONCLUSION: Alterations of miRNA expression in ESCC can be correlated with the presence of common risk factors. The altered expression of certain miRNAs could be used as novel molecular markers of esophageal carcinoma.
Muroi H, Nakajima M, Satomura H, et al.Low PHLDA3 expression in oesophageal squamous cell carcinomas is associated with poor prognosis.
Anticancer Res. 2015; 35(2):949-54 [PubMed
] Related Publications
BACKGROUND/AIM: Patients with oesophageal squamous cell carcinoma (ESCC) have a poor prognosis. Akt has been associated with malignant potential in several cancers, including ESCC. Pleckstrin homology-like domain, family A, member 3 (PHLDA3) has been identified as a direct target gene of p53 and as a potent inhibitor of Akt activation. The present study investigated the role of PHLDA3 expression and its ability to predict prognosis in patients with ESCC who did not receive induction therapy.
MATERIALS AND METHODS: The intensity of PHLDA3 expression was immunohistochemically analyzed in tumor and adjacent normal tissue samples from 84 patients with ESCC, 22 who underwent endoscopic submucosal dissection and 62 who underwent thoracic oesophagectomy.
RESULTS: High expression of PHLDA3 was observed in 60 (71.4%) patients and low expression in 24 (28.6%). Cancer-specific (p=0.029) and disease-free (p<0.001) survival rates were significantly lower in the PHLDA3 low-than in the PHLDA3 high-expression group, and low PHLDA3 expression was an independent predictor of postoperative recurrence (relative risk (RR)=0.38; 95% confidence interval (CI)=0.166-0.78; p=0.0074).
CONCLUSION: Low PHLDA3 expression in ESCC may be predictive of tumor recurrence suggesting that Akt activation may be a therapeutic target in ESCCs.
Okumura T, Shimada Y, Omura T, et al.MicroRNA profiles to predict postoperative prognosis in patients with small cell carcinoma of the esophagus.
Anticancer Res. 2015; 35(2):719-27 [PubMed
] Related Publications
BACKGROUND/AIM: Small cell carcinoma of the esophagus (SCCE) is a rare but very aggressive disease with poor prognosis. The aim of the present study was to identify a molecular signature to predict postoperative outcomes in patients with SCCE.
MATERIALS AND METHODS: Expression of microRNA was detected in surgically-removed SCCE tumors using microarrays. A SCCE cell line (TYUC-1) was established to investigate the biological role of differentially expressed microRNAs.
RESULTS: Hierarchical clustering of microRNA expression revealed two discrete clusters that were identical to the cases with rapid tumor relapse (n=3; median survival, 5.1 months) and the cases with long-term survival (n=3; median observation, 144.7 months), respectively. Eight microRNAs (miR-4323, miR-625, miR-3619-3p, miR-4419b, miR-1249, miR-4648, miR-4664-3p and miR-1203) showed significant correlation with tumor relapse (p<0.01). Migration of TYUC-1 was significantly inhibited by down-regulation of miR-625.
CONCLUSION: The expression profiles of microRNAs in tumors may represent a novel predictor for postoperative outcomes in patients with SCCE.
Brummond NR, Saito YA, Locke GR, et al.Letter: role of GNβ3 polymorphisms in oesophageal adenocarcinoma and gastroesophageal reflux disease.
Aliment Pharmacol Ther. 2015; 41(6):600-1 [PubMed
] Related Publications
Guo W, Wang C, Guo Y, et al.RASSF5A, a candidate tumor suppressor, is epigenetically inactivated in esophageal squamous cell carcinoma.
Clin Exp Metastasis. 2015; 32(1):83-98 [PubMed
] Related Publications
As a result of alternative splicing and differential promoter usage, RASSF5 exists in at least three isoforms (RASSF5A-RASSF5C), which may play different roles in tumorigenesis. The present study was to detect the role of RASSF5A, B and C in esophageal squamous cell carcinoma (ESCC) and clarify the critical CpG sites of RASSF5A, in order to clarify more information on the role of RASSF5 with regard to the pathogenesis of ESCC. Frequent silencing of RASSF5A but not RASSF5B and RASSF5C were found in esophageal cancer cell lines and the silencing of RASSF5A may be reversed by 5-Aza-dC or TSA treatment. The aberrant CpG island 1 methylation of RASSF5A induces silencing of its expression in TE13 cell line. Decreased mRNA and protein expression of RASSF5A was observed in ESCC tumor tissues and was associated with RASSF5A CpG island 1 methylation status. Unlike RASSF5A, expression variation of RASSF5B and RASSF5C was not found in ESCC tissues. Aberrant promoter methylation of RASSF5C was also not found in ESCC. RASSF5A methylation and protein expression were independently associated with ESCC patients' survival. These data indicated that the inactivation of RASSF5A through CpG island 1 methylation may play an important role in ESCC carcinogenesis, RASSF5A may be a functional tumor suppressor and may serve as a prognostic biomarker for ESCC.
Li H, Zhen H, Han L, et al.Association between the genetic variations within TBX21 gene promoter and the clinicopathological characteristics of esophageal squamous cell carcinoma in a high-risk Chinese population.
Tumour Biol. 2015; 36(5):3985-93 [PubMed
] Related Publications
The correlation between TBX21 gene (T-box transcription factor protein 21; T-bet), which was a pivotal transcriptional regulation gene for Th1/Th2 polarization, and the development risk of esophagus squamous cell carcinoma (ESCC) was assessed in a high-risk Chinese population. A total of 302 ESCC cases and 311 normal controls coming from the highest incidence area of China were enrolled in this study. Three polymorphisms at -1499, -1514, and -1993 located in the TBX21 promoter were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Logistic regression was used to determine whether the inherited variations of the TBX21 gene would associate with the risk and the clinicopathological characteristics of ESCC. Among the ESCC patients, an association between the TBX21 -1514T/C or -1993T/C polymorphisms and the lymph node or distant metastasis was found (odds ratios (ORs) were 9.46 and 4.35, respectively, all P < 0.01). By the log-additive model analysis, the results exhibited that three haplotypes, ACC, ACT, and ATC, were significantly related to the development risk of ESCC (OR = 11.81, 3.44, 2.37, respectively, all P < 0.05). TBX21 gene -1514 and -1993 polymorphisms might be counted as the influential factors for lymph node and distant metastasis to ESCC. Especially, the ACC, ACT, and ATC haplotypes derived from the TBX21 gene would increase the susceptibility to ESCC in the high-risk Chinese population.
Tafe LJ, Steinmetz HB, Allen SF, et al.Rapid fluorescence in situ hybridisation (FISH) for HER2 (ERBB2) assessment in breast and gastro-oesophageal cancer.
J Clin Pathol. 2015; 68(4):306-8 [PubMed
] Related Publications
Evaluation of HER2 (ERBB2) gene amplification or protein expression is standard of care in breast (BR) and advanced stage gastro-oesophageal cancers to identify patients eligible for anti-HER2 therapies. Here, we evaluate a rapid fluorescence in situ hybridisation (FISH) technology (HER2 instant quality (IQ) FISH pharmDx Kit) for detection of HER2 in patients with BR and gastro-oesophageal cancer using 30 FFPE samples that had been previously evaluated with the PathVysion HER2 DNA Probe Kit. Cases were scored as positive (HER2:CEN-17 ≥2.0), negative (HER2:CEN-17 <2.0) or equivocal according to the ASCO/CAP 2013 BR cancer guidelines. Ten samples were positive for HER2 amplification while 20 were negative; none were equivocal. The IQ FISH was able to detect low level amplification (HER2:CEN-17 ratio 2.4). The HER2 IQ FISH pharmDx Kit is a FDA approved kit that offers a rapid turnaround time (approximately 3.5 h) and in our laboratory was 100% concordant with prior PathVysion results.
Sherman SK, Maxwell JE, Qian Q, et al.Esophageal cancer in a family with hamartomatous tumors and germline PTEN frameshift and SMAD7 missense mutations.
Cancer Genet. 2015 Jan-Feb; 208(1-2):41-6 [PubMed
] Article available free on PMC
after 01/01/2016 Related Publications
Germline mutations in the PTEN tumor-suppressor gene cause autosomal-dominant conditions such as Cowden and Bannayan-Riley-Ruvalcaba syndromes with variable presentations, including hamartomatous gastrointestinal tumors, dermatologic abnormalities, neurologic symptoms, and elevated cancer risk. We describe a father and son with extensive hamartomatous gastrointestinal polyposis who both developed early-onset esophageal cancer. Exome sequencing identified a novel germline PTEN frameshift mutation (c.568_569insC, p.V191Sfs*11). In addition, a missense mutation of SMAD7 (c.115G>A, p.G39R) with an allele frequency of 0.3% in the Exome Variant Server was detected in both affected individuals. Fluorescence in situ hybridization for PTEN in the resected esophageal cancer specimen demonstrated no PTEN copy loss in malignant cells; however, results of an immunohistochemical analysis demonstrated a loss of PTEN protein expression. While the risks of many cancers are elevated in the PTEN hamartoma tumor syndromes, association between esophageal adenocarcinoma and these syndromes has not been previously reported. Esophageal adenocarcinoma and extensive polyposis/ganglioneuromatosis could represent less common features of these syndromes, potentially correlating with this novel PTEN frameshift and early protein termination genotype. Alternatively, because simultaneous disruption of both the PTEN and TGF-β/SMAD4 pathways is associated with development of esophageal cancer in a mouse model and because SMAD4 mutations cause gastrointestinal hamartomas in juvenile polyposis syndrome, the SMAD7 mutation may represent an additional modifier of these individuals' PTEN-mutant phenotype.
Wang X, Li M, Wang Z, et al.Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration, and invasion of esophageal squamous cell carcinoma cells.
J Biol Chem. 2015; 290(7):3925-35 [PubMed
] Article available free on PMC
after 13/02/2016 Related Publications
MALAT1, a highly conserved long noncoding RNA, is deregulated in several types of cancers. However, its role in esophageal squamous cell carcinoma (ESCC) and its posttranscriptional regulation remain poorly understood. In this study we provide first evidences that a posttranscriptional regulation mechanism of MALAT1 by miR-101 and miR-217 exists in ESCC cells. This posttranscriptional silencing of MALAT1 could significantly suppress the proliferation of ESCC cells through the arrest of G2/M cell cycle, which may be due to MALAT1-mediated up-regulation of p21 and p27 expression and the inhibition of B-MYB expression. Moreover, we also found the abilities of migration and invasion of ESCC cells were inhibited after overexpression of miR-101, miR-217, or MALAT1 siRNA. This might be attributed to the deregulation of downstream genes of MALAT1, such as MIA2, HNF4G, ROBO1, CCT4, and CTHRC1. A significant negative correlation exists between miR-101 or miR-217 and MALAT1 in 42 pairs of ESCC tissue samples and adjacent normal tissues. Mice xenograft data also support the tumor suppressor role of both miRNAs in ESCCs.
Hoekman EJ, Smit VT, Fleming TP, et al.Searching for metastases in ovarian tissue before autotransplantation: a tailor-made approach.
Fertil Steril. 2015; 103(2):469-77 [PubMed
] Related Publications
OBJECTIVE: To exclude minimal residual disease in remaining ovarian tissue after harvesting the ovarian cortex for cryopreservation, by means of a tailor-made approach.
DESIGN: Retrospective case series.
SETTING: Hospital laboratory.
PATIENT(S): We evaluated the ovarian and tubal tissue from 47 cancer patients (breast cancer, [non-]Hodgkin lymphoma; osteo-, Ewing, myxoid lipo-, and oropharyngeal synovial sarcoma; cervical, rectal, and esophageal cancer), who had stored ovarian tissue for fertility preservation.
INTERVENTION(S): Immunohistochemistry (IHC) with tumor-related antibodies and genetic mutation analysis were performed to detect micrometastases by multiple sectioning at three levels of the paraffin-embedded formalin-fixed material. Molecular assays were performed with the use of tissue between these three levels of sectioning.
MAIN OUTCOME MEASURE(S): Detection of micrometastases in ovaries.
RESULT(S): We analyzed 847 ovarian slides to detect isolated tumor cells (ITCs) or micrometastases by IHC. In only one case (1/47) were ITCs detected in the fallopian tube. That patient had an intra-abdominal metastatic esophageal carcinoma. Additional DNA analyses of breast and rectal cancer, Ewing sarcoma, and human papilloma virus in cervical patients did not show evidence of micrometastases in the ovarian tissue.
CONCLUSION(S): The tailor-made approach consisted of patient-specific tumor markers which were used to search for ovarian micrometastases. We found evidence of metastatic disease within the fallopian tube of a patient with intraperitoneal metastatic esophageal adenocarcinoma.
Zhang R, Chen X, Zhang S, et al.Upregulation of miR-494 Inhibits Cell Growth and Invasion and Induces Cell Apoptosis by Targeting Cleft Lip and Palate Transmembrane 1-Like in Esophageal Squamous Cell Carcinoma.
Dig Dis Sci. 2015; 60(5):1247-55 [PubMed
] Related Publications
BACKGROUND: Potential target genes of microRNA (miR)-494 have been reported in many types of cancers. However, the role of miR-494 in esophageal squamous cell carcinoma (ESCC) remains unknown.
AIM: This study focused on the expression and biological function of miR-494 in ESCC.
METHODS: Using bioinformatics analyses, we found that cleft lip and palate transmembrane 1-like (CLPTM1L) was a potential target of miR-494. We performed quantitative real-time (qRT) PCR assays in 37 ESCC tumor tissues to determine the expression of miR-494 and CLPTM1L mRNA, and we analyzed the correlation between both of these factors and clinical characteristics. The cell counting kit-8 and colony formation assays were used to evaluate the effects of miR-494 expression on the proliferation of ESCC cells. The transwell migration assay and flow cytometric apoptosis assay were performed to study the influence of miR-494 on the invasion and apoptosis of ESCC cells. Western blotting, luciferase assays, and CLPTM1L knockdown experiments were used to determine whether CLPTM1L was a target of miR-494.
RESULTS: The qRT-PCR assays showed significant downregulation of miR-494 (P < 0.05) and upregulation of CLPTM1L mRNA (P < 0.05), both of which were significantly associated with lymph node metastases (P < 0.05). High expression of miR-494 inhibited cell proliferation and invasion and promoted cell apoptosis (P < 0.05). The results also showed that CLPTM1L was a target of miR-494.
CONCLUSION: These results show that the expression of miR-494, which can regulate cell growth, invasion and apoptosis of ESCC cells by targeting CLPTM1L, is downregulated in ESCC tumor tissues. The miR-494-CLPTM1L pathway could be further exploited to develop a new approach to treat ESCC.