Correlation of endoplasmic reticulum stress patterns with the immune microenvironment in hepatocellular carcinoma: a prognostic signature analysis

作者全名："Zhan, Ke; Yang, Xin; Li, Shuang; Bai, Yang"

作者地址："[Zhan, Ke; Yang, Xin] Chongqing Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Chongqing, Peoples R China; [Li, Shuang] Chongqing Med Univ, Jinshan Hosp, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China; [Bai, Yang] Chongqing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Chongqing, Peoples R China"

通信作者："Bai, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001128765500001

JCR分区：Q1

影响因子：7.3

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：hepatocellular carcinoma; endoplasmic reticulum stress; prognosis; immune microenvironment; gp6

摘要："Backgrounds The extended duration of endoplasmic reticulum stress (ERS) can impact the progression of hepatocellular carcinoma (HCC) and the efficacy of immunotherapies by interacting with immune cells that have infiltrated the tumor microenvironment (TME).Methods and results The study utilized a training cohort of 364 HCC patients with complete information from The Cancer Genome Atlas Program (TCGA) database, and a validation cohort of 231 HCC patients from the International Cancer Genome Consortium (ICGC) database. The genes related to ERS exhibiting a strong correlation with overall survival (OS) were identified using univariate Cox regression analysis. A 13-gene predictive signature was then produced through the least absolute shrinkage and selection operator (LASSO) regression approach. The data revealed that the ERS-associated gene signature effectively stratified patients into high- or low-risk groups regarding OS in both the training and validation cohorts (P < 0.0001 and P = 0.00029, respectively). Using the multivariate method, it is still an independent prognostic factor in both the training and validation cohorts (P < 0.001 and P = 0.008, respectively). Moreover, several metabolic pathways were identified to be enriched among the 13 genes in the predictive signature. When the ERS-associated gene signature was combined with the tumor-node-metastasis (TNM) stage, the ERS nomogram performed better than either the gene signature or the TNM stage alone (C-index values: 0.731, 0.729, and 0.573, respectively). Further analysis revealed that patients in the high-risk group exhibited increased infiltration of immune cells. Additionally, GP6 was downregulated in HCC tissues among these signature genes (P < 0.05), which was related to poor OS.Conclusions The data suggest that this novel ERS-associated gene signature could contribute to personalized cancer management for HCC. Moreover, targeting GP6 inhibition might be a potential method for HCC therapy."

基金机构：Chongqing Science and Health Joint Medical Research Project [2020FYYX222]

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The present study was funded by the Chongqing Science and Health Joint Medical Research Project (2020FYYX222)."