Oncotarget

Research Papers:

Global proteomic profiling in multistep hepatocarcinogenesis and identification of PARP1 as a novel molecular marker in hepatocellular carcinoma

Xiao Xu, Zhikun Liu, Jianguo Wang, Haiyang Xie, Jie Li, Jili Cao, Lin Zhou and Shusen Zheng _

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Oncotarget. 2016; 7:13730-13741. https://doi.org/10.18632/oncotarget.7316

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Abstract

Xiao Xu1,3,*, Zhikun Liu1,2,*, Jianguo Wang2, Haiyang Xie2, Jie Li2, Jili Cao2, Lin Zhou2, Shusen Zheng1,2,3

1Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

2Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China

3Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China

*These authors have contributed equally to this work

Correspondence to:

Shusen Zheng, e-mail: [email protected]

Keywords: hepatocellular carcinoma, hepatocarcinogenesis, biomarker, PARP1

Received: September 27, 2015     Accepted: January 23, 2016     Published: February 11, 2016

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.


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