Genomic analysis quantifies pyroptosis in the immune microenvironment of HBV-related hepatocellular carcinoma

作者全名："Li, Jiarui; Yu, Jinghui; Zhang, Ting; Pu, Xingyu; Li, Yilan; Wu, Zhongjun"

作者地址："[Li, Jiarui; Li, Yilan; Wu, Zhongjun] First Affiliated Hosp Chongqing Med Univ, Dept Hepatobiliary Surg, Chongqing, Peoples R China; [Yu, Jinghui] Fudan Univ, Coll econ, Dept Int Business, Shanghai, Peoples R China; [Zhang, Ting] First Affiliated Hosp Chongqing Med Univ, Dept PhaseClin Trial Ward 1, Chongqing, Peoples R China; [Pu, Xingyu] West China Hosp Sichuan Univ, Dept Liver Surg, Chengdu, Peoples R China; [Pu, Xingyu] West China Hosp Sichuan Univ, Liver Transplantat Ctr, Chengdu, Peoples R China"

通信作者："Wu, ZJ (通讯作者)，First Affiliated Hosp Chongqing Med Univ, Dept Hepatobiliary Surg, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000838974200001

JCR分区：Q1

影响因子：7.3

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：hepatitis B virus; hepatocellular carcinoma; pyroptosis score; fisetin; tumor immune microenvironment; anti-PD-L1 treatment

摘要："Pyroptosis, a way of pro-inflammatory death, plays a significant part in the tumor microenvironment (TME). A recent study has shown that the hepatitis C virus changes the TME by inducing pyroptosis against hepatocellular carcinoma (HCC). However, compared to TME in hepatitis C virus-infected HCC, the exploration of immune characteristics and response to immunotherapy associated with the pyroptosis phenotype is still insufficient in hepatitis B virus-related HCC (HBV-HCC). Our study constructed pyroptosis-score (PYS) via principal-component analysis (PCA) to unveil the link between pyroptosis and tumor immunity in 369 HBV-HCC patients. Compared with the low-PYS group, subjects with higher PYS were associated with poor prognosis but were more susceptible to anti-PD-L1 treatment. In addition, we found that PYS can serve independently as a prognostic factor for HBV-HCC, making it possible for us to identify specific small molecule drugs with a potential value in inhibiting tumors via targeting pyroptosis. Also, the target genes predicted by the Weighted gene co-expression network analysis (WGCNA) and pharmacophore model were enriched in the HIF-1 signaling pathway and NF-kB transcription factor activity, which were related to the mechanism of inflammation-driven cancer. The PYS is extremely important in predicting prognosis and responses to immunotherapy. New treatment strategies for inflammation-driven cancers may be found by targeting pyroptosis."

基金机构：National Natural Science Foundation of China [81873592]; Chongqing Technology Innovation and Application Development Special Project; [82170666]

基金资助正文："This study was supported by the National Natural Science Foundation of China (No. 82170666 and 81873592), and Chongqing Technology Innovation and Application Development Special Project, Key Project, cstc2021jscx-gksbX0060."