title: Global proteomic profiling in multistep hepatocarcinogenesis and identification of PARP1 as a novel molecular marker in hepatocellular carcinoma.
abstract: The more accurate biomarkers have long been desired for hepatocellular carcinoma (HCC). Here, we characterized global large-scale proteomics of multistep hepatocarcinogenesis in an attempt to identify novel biomarkers for HCC. Quantitative data of 37874 sequences and 3017 proteins during hepatocarcinogenesis were obtained in cohort 1 of 75 samples (5 pooled groups: normal livers, hepatitis livers, cirrhotic livers, peritumoral livers, and HCC tissues) by iTRAQ 2D LC-MS/MS. The diagnostic performance of the top six most upregulated proteins in HCC group and HSP70 as reference were subsequently validated in cohort 2 of 114 samples (hepatocarcinogenesis from normal livers to HCC) using immunohistochemistry. Of seven candidate protein markers, PARP1, GS and NDRG1 showed the optimal diagnostic performance for HCC. PARP1, as a novel marker, showed comparable diagnostic performance to that of classic markers GS and NDRG1 in HCC (AUCs = 0.872, 0.856 and 0.792, respectively). A significant higher AUC of 0.945 was achieved when three markers combined. For diagnosis of HCC, the sensitivity and specificity were 88.2% and 81.0% when at least two of the markers were positive. Similar diagnostic values of PARP1, GS and NDRG1 were confirmed by immunohistochemistry in cohort 3 of 180 HCC patients. Further analysis indicated that PARP1 and NDRG1 were associated with some clinicopathological features, and the independent prognostic factors for HCC patients. Overall, global large-scale proteomics on spectrum of multistep hepatocarcinogenesis are obtained. PARP1 is a novel promising diagnostic/prognostic marker for HCC, and the three-marker panel (PARP1, GS and NDRG1) with excellent diagnostic performance for HCC was established.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Jili
authors.initials: J
authors.lastname: Cao
authors.affiliation: Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism*; D011379:Prognosis; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1
keywords: PARP1; biomarker; hepatocarcinogenesis; hepatocellular carcinoma