Quantitative proteomic analysis identifying three annexins as lymph node metastasis-related proteins in lung adenocarcinoma
Quantitative proteomic analysis identifying three annexins as lymph node metastasis-related proteins in lung adenocarcinoma
复制标题
定量蛋白质组学分析确定三种膜联蛋白为肺腺癌淋巴结转移相关蛋白
DOI：
10.1007/s12032-010-9761-3
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发表时间：
2012-03-01
期刊：
影响因子：
3.4
通讯作者：
Chen, Zhu-Chu
中科院分区：
文献类型：
--
作者：
Liu, Ying-Fu;Chen, Yong-Heng;Chen, Zhu-Chu
淋巴结状态是肺腺癌 (AdC) 患者预后的有力预测指标。为了探索预测肺 AdC 淋巴结转移的新型潜在蛋白质标记物，采用二维差异凝胶电泳 (2D-DIGE) 与质谱 (MS) 相结合，通过激光捕获显微切割 (LCM) 对原发性肺 AdC 和匹配淋巴结 (LN) 转移组织的显微切割癌细胞进行差异蛋白质组分析。鉴定出膜联蛋白（包括膜联蛋白-1、膜联蛋白-2 和膜联蛋白-3），并发现与原发性肺 AdC 相比，在匹配的 LN 转移组织中过度表达。此外，使用免疫组织化学方法评估了石蜡包埋的 188 个原发性肺 AdC 组织和 65 个匹配的阳性淋巴结标本中三种膜联蛋白的差异表达水平。与原发性肺 AdC 相比，在匹配的阳性淋巴结组织中经常观察到annexin-1、annexin-2 和annexin-3 的高表达。在原发性肺AdC中，原发淋巴结阳性AdC组织中三种膜联蛋白的表达水平高于原发淋巴结阴性AdC组织。多因素logistic回归分析显示annexin-1、annexin-2、annexin-3均为淋巴结转移的重要危险因素。此外，统计分析表明annexin-1/annexin-2、annexin-1/annexin-3或annexin-2/annexin-3的同时表达以及所有三种标记物的联合表达与淋巴结转移具有更强的相关性。我们的结果表明，annexin-1、annexin-2 和annexin-3 被确定为与肺 AdC 淋巴结转移相关的潜在生物标志物。
Lymph node status is a strong predictor of outcome for lung adenocarcinoma (AdC) patients. To explore novel potential protein markers for predicting lymph node metastasis of lung AdC, differential proteomic analysis on microdissected cancer cells from primary lung AdC and matched lymph node (LN) metastatic tissues by laser capture microdissection (LCM) was conducted using two-dimensional differential in-gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). Annexins including annexin-1, annexin-2 and annexin-3 were identified and found to be overexpressed in matched LN metastatic tissues compared to primary lung AdC. Furthermore, differential expression levels of the three annexins were evaluated in paraffin-embedded 188 primary lung AdC tissues and 65 matched positive lymph node specimens using immunohistochemistry. High expression of annexin-1, annexin-2, and annexin-3 was all frequently observed in matched positive lymph node tissues compared to primary lung AdC. In primary lung AdC, expression levels of the three annexins in primary lymph node-positive AdC tissues were higher than primary lymph node-negative AdC tissues. Multivariate logistic regression analysis indicated annexin-1, annexin-2, and annexin-3 were all significant risk factors for lymph node metastasis. Furthermore, statistical analysis indicated that the concomitant expression of annexin-1/annexin-2, annexin-1/annexin-3, or annexin-2/annexin-3 and combined expression of all three markers had stronger correlation with lymph node metastasis. Our results suggest that annexin-1, annexin-2, and annexin-3 are identified as potential biomarkers associated with lymph node metastasis in lung AdC.