title: A cancer-array approach elucidates the immune escape mechanism and defects in the DNA repair system in esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Esophageal squamous cell carcinoma (ESCC) is the second-most frequently diagnosed cancer in Northeast Iran, often diagnosed in advanced stages. No standard early diagnostic guideline has been proposed to date and current therapeutic modalities are not effective. Detection of tumor-specific biomarkers, which is the goal of this study, could prove useful in the diagnosis of ESCC.
  
  
  METHODS
  To better understand the gene expression profile of ESCC, we analyzed tumor samples and corresponding adjacent normal tissues from ESCC patients by Chemiluminescent Human Cancer GEArrays. Candidate genes were verified by real-time PCR.
  
  
  RESULTS
  Out of 440 cancer-related genes included in the array, 71 were overexpressed compared to normal tissue, with significant differences in 11 genes. There were 108 genes underexpressed, with significant differences in 5 genes. Until now, the AP2M1, FTL, UBE2L6, HLA-C, and HSPA8 overexpressed genes and XRCC5, TP53I3 and RAP1A underexpressed genes were not reported in ESCC. We chose the MMP2, HLA-G, and XRCC5 markers from 58 Iranian ESCC patients to verify the expression validity by real-time PCR. The microarray results were confirmed with two-tailed significance levels of P = 0.003 (MMP2), P = 0.000 (HLA-G) and P = 0.002(XRCC5). Analysis performed for the candidate genes using GNCpro online software highlighted two pathways, an immuno-modulatory response and DNA replication and repair. We successfully performed and validated Chemiluminescent GEArray gene expression profiling in ESCC. Several biomarkers that might be related to tumorigenesis in ESCC were identified.
  
  
  CONCLUSIONS
  Immuno-modulatory and DNA repair pathways could be used as targets to locate specific diagnostic, prognostic, and therapeutic biomarkers for ESCC.
authors.affiliation: Immunology Research Center and Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ezzat
authors.initials: E
authors.lastname: Dadkhah
authors.forename: Hossein
authors.initials: H
authors.lastname: Naseh
authors.forename: Moein
authors.initials: M
authors.lastname: Farshchian
authors.forename: Bahram
authors.initials: B
authors.lastname: Memar
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Sankian
authors.forename: Reza
authors.initials: R
authors.lastname: Bagheri
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Forghanifard
authors.forename: Mehdi
authors.initials: M
authors.lastname: Montazer
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Kazemi Noughabi
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Hashemi
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Abbaszadegan
mesh_terms: D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D004260:DNA Repair / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D007492:Iran; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D060888:Real-Time Polymerase Chain Reaction; D019139:Tumor Escape / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers