目的分析S100A6在胃癌发展过程中的作用,研究配对胃癌组织以及转移灶中S100A6基因mRNA和蛋白的表达。方法应用实时定量逆转录聚合酶链反应(QRT—PCR)检测20例配对胃癌组织中S100A6mRNA的表达,构建208例胃癌患者配对胃癌组织及转移淋巴结病灶的组织芯片,采用免疫组化方法检测S100A6蛋白的表达,并分析其与临床病理因素以及预后之间的相关性。结果QRT—PCR检测结果显示,20例配对胃癌中,有14例的S100A6mRNA转录水平升高,平均升高倍数为2.25倍。免疫组化检测结果显示,S100A6在正常胃黏膜中的表达阳性率为34.3%,在癌灶中表达阳性率为84.1%,在淋巴结转移灶中表达阳性率为90.9%,癌灶和淋巴结转移灶表达高于正常胃黏膜(P〈0.05)。65.5%的胃癌组织中S100A6表达较对应正常胃黏膜升高。癌灶中S100A6表达与肿瘤大小和侵袭程度相关,肿瘤越大表达越高(P=0.022),侵袭越深表达越高(P=0.000),未发现S100A6表达与其他临床病理因素之间的相关性。S100A6表达与预后无关,但相对于正常胃黏膜,癌灶中S100A6表达升高者的预后比表达下降者差。结论S100A6表达上调是胃癌早期事件,与胃癌的发生、发展相关。
Objective Some members of the S100 gene family have been suggested to be associated with cancer development and metastasis. Our previous eDNA micro-array studies have showed S100A6 expression is elevated in gastric cancer compared with that in paired normal mueosa. To validate our previous results and further investigate the possible role of S100A6 gene in gastric cancer, we carried out this detailed S100A6 expression analysis in more matched gastric cancer samples. Methods S100A6 expression was detected in 20 paired fresh surgical samples of gastric tumor tissue and matched non-cancerous mueosa by QRT-PCR. A gastric cancer tissue mieroarray (TMA) containing 1020 duplicate matched normal mueosa, gastric cancer tissue and metastatic lymph node tissue cores from 208 gastric cancer patients was constructed. S100A6 expression was detected by immunohistochemistry and the correlation between S100A6 expression with elinieopathologieal factors and survival was analyzed. Results As quantitated by QRT-PCR, S100A6 transcript level was elevated in 73.7% of the primary cancer lesions with an average 2.25-fold up-regulation than that in matched non-neoplastic mucosa. As displayed by immunohistechemistry, the positive rate of S100A6 in non-neoplastic mucosa, tumor lesions and metastatic lymph nodes was 34.3% , 84. 1% and 90.9% , respectively. S100A6 expression level in cancer and metastatic lymph node was significantly higher than their matched non-neoplastic mucosa (P 〈 0.05 ). 65.5% of patients showed an increased S100A6 expression in cancer tissue compared with that in matched normal mucosa. S100A6 overexpression was associated with larger tumor size and deeper invasion (P = 0. 022 and P = 0.009). No evidence was found for an association between S100A6 expression level and other variables, including tumor grade, nodal metastases, and TNM stage. There was no association between S100A6 expression level and survival. But compared with paired non-neoplastic mucosa, an increased S100A6 expression in tumor lesion pre