Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma

Frontiers in Pharmacology

Pharmacology

Jiankang Xiang¹  Chuan Liu¹  Pengzhan He¹  Weiguo Dong¹  Qingmin He² 

[1] Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China;Henan Key Laboratory of Helicobacter Pylori and Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China;

关键词: hepatocellular carcinoma;    immunogenic cell death;    prognosis;    tumor microenvironment;    bioinformatics analysis;   

DOI  :  10.3389/fphar.2023.1122011

 received in 2022-12-12, accepted in 2023-03-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Immunogenic cell death (ICD) plays an important role in the development of cancers. This study attempted to explore the role of ICD in the prognosis of hepatocellular carcinoma (HCC).Methods: Gene expression and clinical data were downloaded from The Cancer Genome Alas and Gene Expression Omnibus dataset. The immune/stromal/Estimate scores of the tumor microenvironment (TME) were calculated by ESTIMATE and CIBERSORT algorithms. Kaplan-Meier analysis, functional enrichment analysis, least absolute shrinkage and selection operator (LASSO) analysis, and univariate and multivariate Cox regression analysis were used for prognostic gene screening and prognostic model construction. The correlation of immune cell infiltration and risk scores was analyzed as well. Molecular docking was used to explore the relevance of related genes to anti-cancer drugs.Results: Ten ICD associated differentially expressed genes in HCC were found, and all of them had good predictive ability for HCC. ICD gene high amount of expression group was associated with poor prognosis (p = 0.015). The TME, immune cell infiltration and gene expression were different between ICD high and low groups (all p < 0.05). Six ICD associated genes (BAX, CASP8, IFNB1, LY96, NT5E and PIK3CA) which could predict the survival status were identified and used to construct the prognostic model for HCC. A risk score was calculated and it could be used as an independent prognostic factor in HCC patients (p < 0.001). In addition, the risk score had a positive correlation with macrophage M0 (r = 0.33, p = 0.0086). Molecular docking indicated that sorafenib could bind strongly to the target protein, representing that sorafenib may exert anticancer effects through these six ICD associated genes.Conclusion: This study established a prognostic model including six ICD associated genes for HCC, which may deepen our understanding of ICD and guide therapy for HCC patients.

【 授权许可】

Unknown   
Copyright © 2023 Xiang, Liu, He, He and Dong.