Clinical significance of S100A2 expression in gastric cancer
Clinical significance of S100A2 expression in gastric cancer
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S100A2在胃癌中表达的临床意义
DOI：
10.1007/s13277-013-1495-3
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发表时间：
2014-04-01
期刊：
影响因子：
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通讯作者：
Luo, Chun-Hua
中科院分区：
文献类型：
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作者：
Liu, Ying-Fu;Liu, Qing-Qing;Luo, Chun-Hua
胃癌是世界范围内最常见的恶性肿瘤之一。为了鉴定GC中的候选癌相关生物标志物，在切除的GC组织和匹配的邻近非癌胃组织（ANGT）中进行比较蛋白质组学技术。结果表明，与ANGT相比，S100 A2在GC中被成功地鉴定为显著下调。Western blot分析证实S100 A2表达降低，其表达水平与胃癌分化程度和淋巴结转移状态有关。S100 A2蛋白表达与胃癌分化程度、浸润深度及淋巴结转移密切相关（P <0.05）。Kaplan-Meier曲线显示，随着S100 A2表达水平的降低，无复发概率和总生存率显著降低（P< 0.05）。考克斯回归分析显示S100 A2表达下调是胃癌的一个独立的负性预后指标。通过S100 A2表达载体补充S100 A2蛋白可显著降低MGC-803癌细胞的侵袭数量。然而，通过siRNA干扰敲低S100 A2表达会损害MGC-803细胞的侵袭能力。S100 A2负调控MEK/ERK信号通路，S100 A2下调激活该信号通路可增强MGC-803细胞的体外侵袭能力。结论：S100 A2在胃癌中的表达具有临床意义，S100 A2表达缺失与胃癌的发生、发展密切相关。因此，测定S100 A2表达水平有助于预测GC患者的预后。
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.