Discovery of retinoblastoma-associated binding protein 46 as a novel prognostic marker for distant metastasis in nonsmall cell lung cancer by combined analysis of cancer cell secretome and pleural effusion proteome.
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.
Wang
Chih-Liang
CL
Division of Pulmonary Oncology and Interventional Bronchoscopy, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
Wang
Chun-I
CI
Liao
Pao-Chi
PC
Chen
Chi-De
CD
Liang
Ying
Y
Chuang
Wen-Yu
WY
Tsai
Ying-Huang
YH
Chen
Hua-Chien
HC
Chang
Yu-Sun
YS
Yu
Jau-Song
JS
Wu
Chih-Ching
CC
Yu
Chia-Jung
CJ
D000230:Adenocarcinoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000378:metabolism*; D002465:Cell Movement; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016066:Pleural Effusion, Malignant / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D056524:Retinoblastoma-Binding Protein 7 / Q000097:blood / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D011506:Proteins; D056524:Retinoblastoma-Binding Protein 7