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Open Access 01-12-2022 | Hepatocellular Carcinoma | Research

The POR rs10954732 polymorphism decreases susceptibility to hepatocellular carcinoma and hepsin as a prognostic biomarker correlated with immune infiltration based on proteomics

Authors: Yan Fang, Hongming Yang, Guiming Hu, Jiakun Lu, Jun Zhou, Na Gao, Yuhan Gu, Cunzhen Zhang, Jinhuan Qiu, Yuanyuan Guo, Yunfei Zhang, Qiang Wen, Hailing Qiao

Published in: Journal of Translational Medicine | Issue 1/2022

Abstract

The effect of the cytochrome P450 oxidoreductase (POR) rs10954732 (G > A) polymorphism on hepatocellular carcinoma (HCC) susceptibility is unknown. Here we found that A allele carriers showed a 69% decrease in susceptibility to HCC with overall survival (OS) prolonged to 199%, accompanied by lower activity for cytochrome P450 2E1. A total of 222 differentially expressed proteins were mainly enriched in neutrophil and T cell activation and involved in the immune and inflammatory responses, constituting the altered immune tumor microenvironment related with A allele by proteomics analysis. Hepsin (HPN) showed significant down-regulation in HCC and up-regulation in A allele carriers. A lower HPN level was associated with increased susceptibility to HCC and a worse prognosis. Moreover, HPN is a potential independent prognostic biomarker for HCC and is strongly associated with clinicopathological features, tumor-infiltrating status of immune cells both in our discovery cohort and database surveys. Our findings provide a new potential mechanism by which HPN may play an important role in the susceptibility of rs10954732 A allele carriers to HCC and their prognosis through tumor immune infiltration, thus offering potential insights for future studies on tumor immunotherapy.

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Title: The POR rs10954732 polymorphism decreases susceptibility to hepatocellular carcinoma and hepsin as a prognostic biomarker correlated with immune infiltration based on proteomics
Authors: Yan Fang
Hongming Yang
Guiming Hu
Jiakun Lu
Jun Zhou
Na Gao
Yuhan Gu
Cunzhen Zhang
Jinhuan Qiu
Yuanyuan Guo
Yunfei Zhang
Qiang Wen
Hailing Qiao
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Hepatocellular Carcinoma
Hepatocellular Carcinoma
Biomarkers
Published in: Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-022-03282-1

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