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

Abstract

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.

Characteristic of molecular subtypes based on PANoptosis-related genes and experimental verification of hepatocellular carcinoma

“…Caspase (CASP) is a conserved family member involved in signaling and execution of apoptotic pathways [53]. Its members CASP6 and CASP8 have been shown to be associated with HCC prognosis, mediated by the connexin32 (Cx32)-Src axis, and the inactivation of caspase-8 contributes to the activation of necrotic apoptosis in HCC cells [54][55][56]. MAP3K7 has been reported to affect mTOR phosphorylation and expression levels, and may contribute to HCC tumorigenesis via the MAP3K7-mtor axis [57].…”

A model based on Immunogenic cell death-related genes can predict prognosis and drug sensitivity in patients with hepatocellular carcinoma

“…Similar to us, Lin et al also used 34 ICD genes to divide HCC patients into low ICD and high ICD clusters, and these two groups were signi cantly different in immune status, tumor malignancy and prognosis [22].Our advantage is that by taking the intersection of abnormal genes and ICD subsets of the normal group and HCC, we screened out 6 abnormal genes, which are closely related to tumor progression and ICD, and may be more able to reveal the pathogenesis of tumor. Similarly, Xiang et al used 10 abnormal genes among 34 ICD genes that were different in normal tissues and abnormal tissues to establish prognosis prediction models, but these 10 ICD genes were not all correlated with prognosis [23]. The 6 ICD-related genes we screened are all independent prognostic factors, which may be more closely related to the prognosis of patients with HCC.…”