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

Journal of Translational Medicine

Yunfei Zhang¹  Jun Zhou²  Yan Fang³  Na Gao³  Yuanyuan Guo³  Cunzhen Zhang³  Qiang Wen³  Jiakun Lu³  Guiming Hu³  Jinhuan Qiu³  Hailing Qiao³  Yuhan Gu³  Hongming Yang³ 

[1] Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China;Affiliated People’s Hospital of Zhengzhou University, Zhengzhou, China;Institute of Clinical Pharmacology, Zhengzhou University, 450052, Zhengzhou, China;

关键词: Hepatocellular carcinoma;    POR;    Polymorphisms;    HPN;    Proteomics;   

DOI  :  10.1186/s12967-022-03282-1

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY