title: Secretory/releasing proteome-based identification of plasma biomarkers in HBV-associated hepatocellular carcinoma.
abstract: For successful therapy, hepatocellular carcinoma (HCC) must be detected at an early stage. Herein, we used a proteomic approach to analyze the secretory/releasing proteome of HCC tissues to identify plasma biomarkers. Serum-free conditioned media (CM) were collected from primary cultures of cancerous tissues and surrounding noncancerous tissues. Proteomic analysis of the CM proteins permitted the identification of 1365 proteins. The enriched molecular functions and biological processes of the CM proteins, such as hydrolase activity and catabolic processes, were consistent with the liver being the most important metabolic organ. Moreover, 19% of the proteins were characterized as extracellular or membrane-bound. For validation, secretory proteins involved in transforming growth factor-β signaling pathways were validated in plasma samples. Alphafetoprotein (AFP), metalloproteinase (MMP)1, osteopontin (OPN), and pregnancy-specific beta-1-glycoprotein (PSG)9 were significantly increased in HCC patients. The overall performance of MMP1 and OPN in the diagnosis of HCC remained greater than that of AFP. In addition, this study represents the first report of MMP1 as a biomarker with a higher sensitivity and specificity than AFP. Thus, this study provides a valuable resource of the HCC secretome with the potential to investigate serological biomarkers. MMP1 and OPN could be used as novel biomarkers for the early detection of HCC and to improve the sensitivity of biomarkers compared with AFP.
authors.affiliation: State Key Laboratory of Molecular Oncology, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, Cancer Institute (Hospital), Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Weiqi
authors.initials: W
authors.lastname: Rong
authors.forename: Ting
authors.initials: T
authors.lastname: Xiao
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.forename: Xiuying
authors.initials: X
authors.lastname: Zhao
authors.forename: Hongxia
authors.initials: H
authors.lastname: Wang
authors.forename: Naijun
authors.initials: N
authors.lastname: Han
authors.forename: Suping
authors.initials: S
authors.lastname: Guo
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Wu
authors.forename: Yanning
authors.initials: Y
authors.lastname: Gao
authors.forename: Shujun
authors.initials: S
authors.lastname: Cheng
mesh_terms: D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology*; D019295:Computational Biology; D017077:Culture Media, Conditioned / Q000737:chemistry; D016895:Culture Media, Serum-Free / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000821:virology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000821:virology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008875:Middle Aged; D009924:Organ Culture Techniques; D053495:Osteopontin / Q000378:metabolism; D011268:Pregnancy-Specific beta 1-Glycoproteins / Q000378:metabolism; D020543:Proteome; D040901:Proteomics; D012372:ROC Curve; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D011268:Pregnancy-Specific beta 1-Glycoproteins; D020543:Proteome; D016212:Transforming Growth Factor beta; D000509:alpha-Fetoproteins; D053495:Osteopontin; D020781:Matrix Metalloproteinase 1