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

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.

DNA methylation in peripheral blood leukocytes for the association with glucose metabolism and invasive breast cancer

“…Although the methylation levels of the CpGs in relation to IR and BC that are common across Chr, CpG contexts, and the gene regions were comparable between the WHI and TCGA cohorts, only 1 individual IR-CpG (cg01676795 in POR ) was common in its relationship to BC risk in both cohorts. P450 oxidoreductase (POR) gene expression has been studied in few cancer types, presenting significant overall suppression of POR expression in muscle-invasive bladder cancer [ 86 ] and differentially expressed gene proteins enriched in neutrophil and T cell activation in hepatocellular carcinoma [ 87 ]; those findings support the important role of POR in carcinogenesis via alteration of the immune tumor microenvironment. Our finding of this CpG in POR in association with BC risk is novel, which calls for a future study on the methylation in this gene linked to BC by taking into account the effects of nearby SNPs.…”

KIAA1429 facilitates progression of hepatocellular carcinoma by modulating m6A levels in HPN

“…HPN is a transmembrane serine protease implicated in numerous biological processes including auditory nerve development, hepatocyte growth, adipocyte differentiation, urinary protein secretion, and cancer metastasis [ 33 , 34 ]. According to the relevant literature, HPN is expressed at low levels in LIHC and is a potential independent prognostic biomarker for LIHC [ 35 , 36 ]. Low hepsin expression is associated with poor survival [ 37 ].…”