Liu Ying-Fu, Liu Qing-Qing, Wang Xuan, Luo Chun-Hua
Department of Basic Medical Sciences, Medical College, Xiamen University, Xiangan South Road, Xiangan District, 361102, Xiamen, Fujian, China,
Tumour Biol. 2014 Apr;35(4):3731-41. doi: 10.1007/s13277-013-1495-3. Epub 2013 Dec 7.
Gastric carcinoma (GC) is one of the most common malignancies worldwide. To identify the candidate carcinoma-related biomarker in GC, comparative proteome technique was performed in resected GC tissues and matched adjacent non-cancerous gastric tissues (ANGT). As a result, S100A2 was successfully identified to be down-regulated significantly in GC compared with ANGT. Western blot analysis validated decreased expression of S100A2, and its expression level was related with the degree of tumor differentiation and status of lymph node metastasis in GC. Furthermore, immunohistochemistry analysis showed S100A2 down-expression was significantly associated with poor differentiation (P < 0.05), advanced depth of invasion (P < 0.05) and lymph node metastasis (P < 0.05) in GC. Kaplan-Meier curves showed that the relapse-free probability and the overall survival rate were significantly decreased with S100A2 expression decreasing (P < 0.05). Cox regression analysis indicated S100A2 down-expression was a negative independent prognostic biomarker for GC. A supplement of S100A2 protein by S100A2 expression vector significantly decreased the number of invaded cancer cells MGC-803. However, knockdown of S100A2 expression by siRNA interference compromised the invasion ability of MGC-803 cells. Moreover, S100A2 negatively regulated MEK/ERK signaling pathway, and activation of this signaling pathway by S100A2 down-regulation increased in vitro invasion of MGC-803 cells. In conclusion, this study demonstrated the clinical significance of S100A2 expression in GC, and loss of S100A2 expression contributes to GC development and progression. Therefore, the determination of S100A2 expression levels contributes to predict the outcome of GC patients.
胃癌（GC）是全球最常见的恶性肿瘤之一。为了鉴定胃癌中潜在的癌相关生物标志物，我们对手术切除的胃癌组织及配对的癌旁非癌胃组织（ANGT）进行了比较蛋白质组学技术研究。结果显示，与ANGT相比，S100A2在胃癌组织中成功被鉴定为显著下调。蛋白质免疫印迹分析证实了S100A2表达降低，且其表达水平与胃癌的肿瘤分化程度及淋巴结转移状态相关。此外，免疫组织化学分析表明，S100A2低表达与胃癌的低分化（P < 0.05）、浸润深度增加（P < 0.05）及淋巴结转移（P < 0.05）显著相关。Kaplan-Meier曲线显示，随着S100A2表达降低，无复发生存概率和总生存率显著下降（P < 0.05）。Cox回归分析表明，S100A2低表达是胃癌的一个独立负性预后生物标志物。通过S100A2表达载体补充S100A2蛋白可显著减少MGC-803侵袭癌细胞的数量。然而，通过小干扰RNA（siRNA）干扰敲低S100A2表达会损害MGC-803细胞的侵袭能力。此外，S100A2负向调节MEK/ERK信号通路，S100A2表达下调激活该信号通路会增加MGC-803细胞的体外侵袭能力。总之，本研究证明了S100A2表达在胃癌中的临床意义，S100A2表达缺失促进了胃癌的发生和发展。因此，检测S100A2表达水平有助于预测胃癌患者的预后。
