Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Oncol Rep. 2013 Jul;30(1):111-8. doi: 10.3892/or.2013.2419. Epub 2013 Apr 23.
Overexpression of the S100 calcium-binding protein A4 (S100A4) is involved in epithelial-to-mesenchymal transition, oncogenic transformation, angiogenesis, cytoskeletal integrity and cancer metastasis. Here, we elucidated the role of S100A4 in tumorigenesis and progression of gastric carcinomas. S100A4 expression in gastric carcinomas, adenomas and adjacent non-neoplastic mucosa was analyzed by immunohistochemical, real-time reverse transcriptase (RT)-polymerase chain reaction (PCR) and western blot analyses, and was correlated with various clinicopathological parameters. S100A4 protein expression was increased gradually in the following order: gastritis (19.2%), intestinal metaplasia (IM; 23.3%), dysplasia (34.9%) and carcinoma (55.2%; P<0.001). S100A4 was positively correlated with tumor size, depth of invasion, lymphatic invasion, lymph node metastasis and tumor-node-metastasis (TNM) staging (P<0.05), but not with the age and gender of the carcinoma patients (P>0.05). Intestinal-type (IT) carcinomas showed a higher S100A4 expression than diffuse-type (DT) carcinomas (P<0.001). S100A4 mRNA expression also increased in the following order: gastritis < IM < dysplasia < carcinoma (P<0.05). S100A4 overexpression was observed in gastric carcinomas with a larger diameter, deeper invasion, lymph node metastasis and in IT carcinoma (P<0.05). Univariate analysis using the Kaplan-Meier method indicated a lower cumulative survival rate for patients with weak or moderate S100A4 expression compared with patients not expressing S100A4 (P<0.001). Multivariate analysis using Cox's proportional hazard model demonstrated that depth of invasion, lymphatic or venous invasion, lymph node metastasis, TNM staging and S100A4 expression were independent factors for poor patient prognosis (P<0.05). In conclusion, S100A4 upregulation is positively associated with the pathogenesis, growth, invasion, metastasis and differentiation of gastric carcinomas. S100A4 may be a promising marker indicative of the aggressive behavior and prognosis of gastric carcinomas.
S100 钙结合蛋白 A4（S100A4）的过表达与上皮间质转化、致癌转化、血管生成、细胞骨架完整性和癌症转移有关。在这里，我们阐明了 S100A4 在胃癌发生和进展中的作用。通过免疫组织化学、实时逆转录（RT）-聚合酶链反应（PCR）和 Western blot 分析分析了 S100A4 在胃癌、腺瘤和相邻非肿瘤黏膜中的表达，并与各种临床病理参数相关。S100A4 蛋白表达按以下顺序逐渐增加：胃炎（19.2%）、肠上皮化生（IM；23.3%）、发育不良（34.9%）和癌（55.2%；P<0.001）。S100A4 与肿瘤大小、浸润深度、淋巴浸润、淋巴结转移和肿瘤-淋巴结-转移（TNM）分期呈正相关（P<0.05），但与癌患者的年龄和性别无关（P>0.05）。肠型（IT）癌的 S100A4 表达高于弥漫型（DT）癌（P<0.001）。S100A4 mRNA 表达也按以下顺序增加：胃炎<IM<发育不良<癌（P<0.05）。S100A4 过表达见于直径较大、浸润较深、淋巴结转移和 IT 癌的胃癌（P<0.05）。Kaplan-Meier 方法的单因素分析表明，与不表达 S100A4 的患者相比，S100A4 表达弱或中度的患者累积生存率较低（P<0.001）。Cox 比例风险模型的多因素分析表明，浸润深度、淋巴或静脉浸润、淋巴结转移、TNM 分期和 S100A4 表达是患者预后不良的独立因素（P<0.05）。总之，S100A4 的上调与胃癌的发病机制、生长、浸润、转移和分化呈正相关。S100A4 可能是一种有前途的标志物，提示胃癌的侵袭性行为和预后。
