Identification of serologic biomarkers for predicting microvascular invasion in hepatocellular carcinoma
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Yuan-Quan Yu1,*, Liang Wang1,*, Yun Jin1, Jia-Le Zhou1, Yan-Hua Geng2, Xing Jin1, Xiao-Xiao Zhang1, Jun-Jie Yang1, Cheng-Ming Qian1, Dong-Er Zhou1, Da-Ren Liu1, Shu-You Peng1, Yan Luo3, Lei Zheng4, Jiang-Tao Li1
1Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
2Department of Pathology, The Red Cross Hospital in Hangzhou, Hangzhou, Zhejiang, China
3Center for Cancer Research and Department of Biochemistry, Zhejiang University School of Basic Medical Sciences, Hangzhou, Zhejiang, China
4The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
*These authors have contributed equally to this work
Jiang-Tao Li, e-mail: firstname.lastname@example.org
Lei Zheng, e–mail: email@example.com
Yan Luo, e–mail: firstname.lastname@example.org
Keywords: hepatocellular carcinoma, microvascular invasion, sero-proteomics, biomarker, diagnosis
Received: September 08, 2015 Accepted: February 05, 2016 Published: February 23, 2016
Microvascular invasion (MVI) of hepatocellular carcinoma (HCC) is a major risk factor for early recurrence and poor survival after curative surgical therapies. However, MVI can only be diagnosed by pathological examination following resection. The aim of this study is to identify serologic biomarkers for predicting MVI preoperatively to help facilitate treatment decisions. We used the sero-proteomic approach to identify antigens that induce corresponding antibody responses either specifically in the serum from MVI (+) patients or from MVI (−) patients. Six antigens were subsequently identified as HSP 70, HSP 90, alpha-enolase (Eno-1), Annexin A2, glutathione synthetase and beta-actin by mass spectrometry. The antibodies titers in sera corresponding to four of these six antigens were measured by ELISA and compared between 35 MVI (+) patients and 26 MVI (−) patients. The titers of anti-HSP 70 antibodies were significantly higher in MVI (−) patients than those in MVI (+) patients; and the titers of anti-Eno-1 antibodies were significantly lower in MVI (−) patients than those in MVI (+) patients. The results were subjected to multivariate analysis together with other clinicopathologic factors, suggesting that antibodies against HSP 70 and Eno-1 in sera are potential biomarkers for predicting MVI in HCC prior to surgical resection. These biomarkers should be further investigated as potential therapeutic targets.
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