S100A16 is a Prognostic Marker for Lung Adenocarcinomas.
S100A16 is a Prognostic Marker for Lung Adenocarcinomas.
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DOI：
10.7314/apjcp.2015.16.16.7039
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Keita Saito;Makoto Kobayashi;R. Nagashio;S. Ryuge;K. Katono;Hiroyasu Nakashima;B. Tsuchiya;Shi‐Xu Jiang;M. Saegusa;Y. Satoh;N. Masuda;Yuichi Sato
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文献类型：
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作者：
Keita Saito;Makoto Kobayashi;R. Nagashio;S. Ryuge;K. Katono;Hiroyasu Nakashima;B. Tsuchiya;Shi‐Xu Jiang;M. Saegusa;Y. Satoh;N. Masuda;Yuichi Sato
背景低分子量蛋白质和多肽中包含许多控制多种细胞功能的功能分子。材料和方法为了鉴定肺腺癌（AC）中控制功能的蛋白，我们在二维上使用tricine- sds聚丙烯酰胺（tricine 2-DE）进行了二维凝胶电泳。该系统能够检测1 kDa以下的蛋白，即使有翻译后修饰。为了证实检测到的蛋白作为AC的新型肿瘤标志物的有效性，我们对170个经福尔马林固定和石蜡包埋的肺AC组织进行了免疫组织化学分析。结果Tricine 2-DE结果显示，与肺鳞状细胞癌、小细胞癌和大细胞神经内分泌癌源性细胞相比，肺ac源性细胞中S100A16等5种蛋白过表达。免疫组化结果显示，S100A16在肺癌组织中表现出多种亚细胞定位，膜染色状态与t因子（P=0.0008）、病理分期（P=0.0015）、分化程度（P=0.0001）、淋巴浸润（P=0.0007）、血管浸润（P=0.0001）、胸膜浸润（P=0.0087）、性别（P=0.039）相关，与年龄、吸烟史无关。更重要的是，S100A16的膜性染色与I期（P=0.0088）或II / III期（P=0.0003）肺AC患者较差的总生存率显著相关，多因素分析证实S100A16的膜性表达是一个独立的不良预后指标（P=0.0001）。结论S100A16蛋白是一种新的肺AC预后指标。
BACKGROUND Many functional molecules controlling diverse cellular function are included in low-molecular weight proteins and peptides. MATERIALS AND METHODS To identify proteins controlling function in lung adenocarcinomas (AC), we performed two-dimensional gel electrophoresis employing tricine-SDS polyacrylamide in the second dimension (tricine 2-DE). This system was able to detect proteins under 1 kDa even with post- translational modifications. To confirm the utility of detected proteins as novel tumor markers for AC, we performed immunohistochemical analysis using 170 formalin-fixed and paraffin-embedded lung AC tissues. RESULTS Tricine 2-DE revealed that five proteins including S100A16 were overexpressed in lung AC-derived cells compared with lung squamous cell carcinoma, small cell carcinoma, and large cell neuroendocrine carcinoma- derived cells. Immunohistochemically, S100A16 showed various subcellular localization in lung cancer tissues and a membranous staining status was correlated with the T-factor (P=0.0008), pathological stage (P=0.0015), differentiation extent (P=0.0001), lymphatic invasion (P=0.0007), vascular invasion (P=0.0001), pleural invasion (P=0.0087), and gender (P=0.039), but not with the age or smoking history. More importantly, membranous staining of S100A16 was significantly correlated with a poorer overall survival of either stage I (P=0.0088) or stage II / III (P=0.0003) lung AC patients, and multivariate analysis confirmed that membranous expression of S100A16 was an independent adverse prognostic indicator (P=0.0001). CONCLUSIONS The present results suggest that S100A16 protein is a novel prognostic marker for lung AC.