Immunology Research Center and Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Arch Iran Med. 2013 Aug;16(8):463-70.
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.
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.
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.
Immuno-modulatory and DNA repair pathways could be used as targets to locate specific diagnostic, prognostic, and therapeutic biomarkers for ESCC.
食管鳞状细胞癌（ESCC）是伊朗东北部第二大常见癌症，通常在晚期诊断。迄今为止，尚未提出任何标准的早期诊断指南，而且目前的治疗方法并不有效。本研究旨在检测肿瘤特异性生物标志物，如果成功，这将有助于 ESCC 的诊断。
为了更好地了解 ESCC 的基因表达谱，我们通过 Chemiluminescent Human Cancer GEArrays 分析了 ESCC 患者的肿瘤样本及其相应的相邻正常组织。通过实时 PCR 验证候选基因。
在阵列中包含的 440 个癌症相关基因中，有 71 个与正常组织相比表达上调，其中 11 个基因差异有统计学意义。有 108 个基因表达下调，其中 5 个基因差异有统计学意义。到目前为止，AP2M1、FTL、UBE2L6、HLA-C 和 HSPA8 这 5 个过表达基因以及 XRCC5、TP53I3 和 RAP1A 这 3 个低表达基因在 ESCC 中尚未有报道。我们从 58 名伊朗 ESCC 患者中选择了 MMP2、HLA-G 和 XRCC5 标志物，通过实时 PCR 验证表达的有效性。微阵列结果与双尾显著性水平 P = 0.003（MMP2）、P = 0.000（HLA-G）和 P = 0.002（XRCC5）相吻合。使用 GNCpro 在线软件对候选基因进行分析，突出了两个途径，即免疫调节反应和 DNA 复制和修复。我们成功地对 ESCC 进行了 Chemiluminescent GEArray 基因表达谱分析，并验证了其结果。鉴定出了一些可能与 ESCC 肿瘤发生有关的生物标志物。
免疫调节和 DNA 修复途径可作为定位 ESCC 特定诊断、预后和治疗生物标志物的靶点。
