Division of Pulmonary Oncology and Interventional Bronchoscopy, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
J Proteome Res. 2009 Oct;8(10):4428-40. doi: 10.1021/pr900160h.
Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer, which is one of the most prominent causes of cancer-related mortality worldwide. Discovery of serum tumor markers could facilitate early NSCLC detection and metastatic prognosis. Here, we simultaneously analyzed the NSCLC cell secretome and proteomic profiles of pleural effusion from lung adenocarcinoma patients for NSCLC biomarker discovery. Retinoblastoma-associated binding protein 46 (RbAp46), one of the proteins detected both in NSCLC cell secretome and pleural effusion proteome, was chosen for further evaluation. Both of RbAp46 mRNA and protein levels were upregulated significantly in NSCLC cancer tissues. Serum levels of RbAp46 were markedly higher in NSCLC patients than in healthy controls, and a combination of RbAp46 and CEA could outperform CEA alone in discriminating NSCLC patients from healthy persons. Importantly, elevated serum RbAp46 level was highly correlated with NSCLC distant metastasis. Moreover, knockdown of RbAp46 inhibited the migration ability of lung cancer cells. Our data collectively suggest that RbAp46 serves as a novel biomarker and prognosticator for NSCLC, and is involved in lung cancer cell migration.
非小细胞肺癌（NSCLC）是最常见的肺癌类型，也是全球癌症相关死亡率的主要原因之一。血清肿瘤标志物的发现可以促进 NSCLC 的早期检测和转移预后。在这里，我们同时分析了来自肺腺癌患者胸腔积液的 NSCLC 细胞分泌组和蛋白质组谱，以发现 NSCLC 生物标志物。视网膜母细胞瘤相关结合蛋白 46（RbAp46）是在 NSCLC 细胞分泌组和胸腔积液蛋白质组中都检测到的蛋白质之一，被选为进一步评估的对象。RbAp46 的 mRNA 和蛋白水平在 NSCLC 癌组织中均显著上调。与健康对照组相比，NSCLC 患者的血清 RbAp46 水平明显升高，并且 RbAp46 和 CEA 的组合在区分 NSCLC 患者和健康人方面优于 CEA 单独使用。重要的是，血清 RbAp46 水平升高与 NSCLC 远处转移高度相关。此外，RbAp46 的敲低抑制了肺癌细胞的迁移能力。我们的数据表明，RbAp46 是 NSCLC 的一种新型生物标志物和预后标志物，并且参与了肺癌细胞的迁移。
