Post-surgical resection prognostic value of combined OPN, MMP7, and PSG9 plasma biomarkers in hepatocellular carcinoma

Abstract

Biomarkers for hepatocellular carcinoma (HCC) following curative resection are not currently sufficient for prognostic indication of overall survival (OS) and disease-free survival (DFS). The aim of this study was to investigate the prognostic performance of osteopontin (OPN), matrix metalloproteinase 7 (MMP7), and pregnancy specific glycoprotein 9 (PSG9) in patients with HCC. A total of 179 prospective patients with HCC provided plasma before hepatectomy. Plasma OPN, MMP7, and PSG9 levels were determined by enzyme-linked immunosorbent assay. Correlations between plasma levels, clinical parameters, and outcomes (OS and DFS) were overall analyzed. High OPN (≥149.97 ng/mL), MMP7 (≥2.28 ng/mL), and PSG9 (≥45.59 ng/mL) were prognostic indicators of reduced OS (P<0.001, P<0.001, and P=0.007, respectively). Plasma PSG9 protein level was an independent factor in predicting OS (P=0.008) and DFS (P=0.038). Plasma OPN+MMP7+PSG9 elevation in combination was a prognostic factor for OS (P<0.001). OPN was demonstrated to be a risk factor-associated OS in stage I patients with HCC and patients with low α-fetoprotein levels (<20 ng/mL). These findings suggested that OPN, MMP7, PSG9 and their combined panels may be useful for aiding in tumor recurrence and mortality risk prediction of patients with HCC, particularly in the early stage of HCC carcinogenesis.

Keywords

biomarkers / OPN / MMP7 / PSG9 / HCC / prognosis

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Acknowledgements

This work was supported by grants from the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2016-I2M-1-001), the National Natural Science Foundation of China (No. 81172035), and the National High Technology Research and Development Program of China (No. 2012AA020206).

Compliance with ethics guidelines

Weiqi Rong, Yang Zhang, Lei Yang, Lin Feng, Baojun Wei, Fan Wu, Liming Wang, Yanning Gao, Shujun Cheng, Jianxiong Wu, and Ting Xiao declare no conflicts of interests. All procedures related to human samples were approved by the Review Board of Chinese Academy of Medical Sciences Cancer Institute. All sample donors provided informed consent, and the study was conducted under the approval of the Institutional Ethics Committee.

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