Paper Information

Journal:   ARCHIVES OF IRANIAN MEDICINE   AUGUST 2013 , Volume 16 , Number 8; Page(s) 463 To 470.
 
Paper: 

A CANCER-ARRAY APPROACH ELUCIDATES THE IMMUNE ESCAPE MECHANISM AND DEFECTS IN THE DNA REPAIR SYSTEM IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

 
DOI: 

013168/AIm.006

 
Author(s):  DADKHAH EZZAT, NASEH HOSSEIN, FARSHCHIAN MOEIN, MEMAR BAHRAM, SANKIAN MOJTABA, BAGHERI REZA, FORGHANIFARD MOHAMMAD MAHDI, MONTAZER MEHDI, KAZEMI NOUGHABI MAHBOOBEH, HASHEMI MEHRDAD, ABBASZADEGAN MOHAMMAD REZA*
 
* MEDICAL GENETICS RESEARCH CENTER & DIVISION OF HUMAN GENETICS IMMUNOLOGY RESEARCH CENTER, AVICENNA RESEARCH INSTITUTE, MASHHAD UNIVERSITY OF MEDICAL SCIENCES, MASHHAD
 
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 tissue 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.
CONCLUSION: Immuno-modulatory and DNA repair pathways could be used as targets to locate specific diagnostic, prognostic, and therapeutic biomarkers for ESCC.

 
Keyword(s): BIOMARKER, DNA REPAIR, ESCC, GENE EXPRESSION, IMMUNE ESCAPE, PROFILING
 
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