Development of a novel protein biomarker panel for lung cancer by integration of cancer cell secretome & pleural effusion proteome

• Main Authors: Yu Ming Deng, 鄧育旻
• Other Authors: C. J. Yu
• Format: Others
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/01064472826294349514

碩士 === 長庚大學 === 生物醫學研究所 === 98 === Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, which is one of the most prominent causes of cancer-related mortality in Taiwan (17.5%). In this study, we integrate two adenocarcinoma cancer cell lines secretome, CL1-0, CL1-5 and human pleural effusion proteome from lung adenocarcinoma patients to discover serum/pleural effusion maker panel for NSCLC. Previously, we have generated two of lung adenocarcinoma cell lines secretome databases and one pleural effusion proteome database by one-dimensional gel electrophoresis in conjunction with nano liquid-chromatography tandem mass spectrometry (GeLC-MS/MS) platform. After integration of these three protein datasets, we found 163 proteins identified in all of these three datasets. The 163 identified proteins were further analyzed by bioinformatics software programs and 89 candidates are predicted as secreted protein. Based on literature search, we selected four potential markers, including angiogenin, cystatin-C, fetuin-A and IGFBP2 for further verification by using human sera and pleural effusions. Our results showed that the serum levels of angiogenin and IGFBP2 in NSCLC patients were significantly higher than those in healthy controls, whereas, serum level of fetuin-A was significantly decreased in NSCLC patients as compared to healthy controls. The area under curve (AUC) value for angiogenin, cystatin-C, fetuin-A, IGFBP2 and CEA was 0.61, 0.62, 0.73, 0.71 and 0.71, respectively. A combination of serum fetuin-A, IGFBP2 and CEA displayed higher diagnostic capacity (AUC 0.79) than either marker alone. The AUC value for IGFBP2, fetuin-A and CEA for prediction of disease stage (stage I/II vs. stage III/IV) was 0.69, 0.57 and 0.59, respectively. These results indicate IGFBP2 is a potential maker to distinguish disease stage. Importantly, protein level of IGFBP2 in malignant pleural effusion from cancer patients was significantly higher than those from patients without malignancy. We also characterized biological significance of secreted proteins in lung cancer progress. We found that extracellular fetuin-A inhibite cellular migration and extracellular IGFBP2 promote cellular migration of lung cancer cells. Collectively, our results suggest that integration of cancer cell secretome and pleural effusion proteome provide an efficient means of identifying novel marker panel for NSCLC.