The POR rs10954732 polymorphism decreases susceptibility to hepatocellular carcinoma and hepsin as a prognostic biomarker correlated with immune infiltration based on proteomics.
The POR rs10954732 polymorphism decreases susceptibility to hepatocellular carcinoma and hepsin as a prognostic biomarker correlated with immune infiltration based on proteomics.
复制标题
POR rs10954732 多态性降低了对肝细胞癌的易感性，并且 hepsin 作为基于蛋白质组学的与免疫浸润相关的预后生物标志物。
DOI：
10.1186/s12967-022-03282-1
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发表时间：
2022-02-14
影响因子：
7.4
通讯作者：
Qiao H
中科院分区：
文献类型：
--
作者：
Fang Y;Yang H;Hu G;Lu J;Zhou J;Gao N;Gu Y;Zhang C;Qiu J;Guo Y;Zhang Y;Wen Q;Qiao H
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. The online version contains supplementary material available at 10.1186/s12967-022-03282-1.
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DOI：
10.1038/nrg.2018.4
发表时间：
2018-05
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Karczewski KJ;Snyder MP
通讯作者：
Snyder MP
基因多态性和细胞色素P450含量对人肝微粒体代谢活动的影响有限
影响因子：
4.6
作者：
Gao, Na;Tian, Xin;Qiao, Hailing
通讯作者：
Qiao, Hailing
从肝纤维化到肝癌：较高的细胞色素 P450 2E1 活性是潜在的危险因素
影响因子：
4.6
作者：
Gao, Jie;Wang, Zhao;Qiao, Hai-Ling
通讯作者：
Qiao, Hai-Ling
影响因子：
6.7
作者：
Chen, Chien-Hung;Su, Kang-Yi;Sheu, Jin-Chuan
通讯作者：
Sheu, Jin-Chuan
影响因子：
4.1
作者：
Miller WL;Agrawal V;Sandee D;Tee MK;Huang N;Choi JH;Morrissey K;Giacomini KM
通讯作者：
Giacomini KM