A novel prognostic index of hepatocellular carcinoma based on immunogenomic landscape analysis

Abstract

Changes in immune responses to hepatocellular carcinoma (HCC) are closely related to the occurrence, development, and prognosis of this disease. Exploring the role of immune‐related genes (IRGs) in HCC would provide insights into the mechanisms regulating this disease. The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) provide a platform for such research, owing to a large number of HCC samples available for comprehensive and systematic immunogenomics analyses. We analyzed the IRGs expression profile and clinical information of patients with HCC based on the TCGA and ICGC database. Potential molecular mechanisms and properties of the screened IRGs were analyzed across multiple databases. And we analyzed the correlation between IRGs, single‐nucleotide polymorphisms, and copy number variation. A novel prognostic index, based on IRGs, was developed using the LASSO Cox regression algorithm, followed by univariate and multivariate Cox regression analyses to analyze the prognostic index. Information in the ICGC database was used to verify the reliability of the prognostic index. A total of 54 differentially expressed IRGs were found to be significantly associated with HCC prognosis, and there is a significant correlation between their expression level and copy number variation. Functional enrichment analyses indicated that the genes play active roles in tumor and immune‐related signaling pathways. In addition, five potential biomarkers namely IRG, MAPK3, HSP90AA1, HSP90AB1, HSPA4, and CDK4, were identified. Finally, a novel prognostic index, based on IRGs (PSMD14, FABP6, ISG20L2, HGF, BIRC5, IL17D, and STC2), was found useful as an independent prognostic factor, not only for prognosis but also to reflect levels of infiltration in a variety of immune cells. Our team conducted a genomics study of IRGs in HCC and screened several clinically significant IRGs, and our model provides an effective approach for stratification and characterization of patients using IRG‐based immunolabeling tools to monitor the prognosis of HCC.

Identification of Key Genes With Differential Correlations in Lung Adenocarcinoma

“…Interferon-stimulated 20-kDa exonuclease-like 2 (ISG20L2) is a novel vertebrate nucleolar exoribonuclease and involved in ribosome biogenesis ( Couté et al, 2008 ; Simabuco et al, 2012 ). As one of target genes regulated by miR-139-3p, ISG20L2 has recently been related to hepatocellular carcinoma prognosis ( Zhu et al, 2019 ), consistent with an immunogenomic landscape study which adds the roles of ISG20L2 in reflecting levels of infiltration in diverse immune cells ( Xiao et al, 2021 ). Additionally, high expression of ISG20L2 has been found in several cancers and affected cancer occurrence in a variety of aspects ( Xu et al, 2020 ; Xiao et al, 2021 ).…”

“…As one of target genes regulated by miR-139-3p, ISG20L2 has recently been related to hepatocellular carcinoma prognosis ( Zhu et al, 2019 ), consistent with an immunogenomic landscape study which adds the roles of ISG20L2 in reflecting levels of infiltration in diverse immune cells ( Xiao et al, 2021 ). Additionally, high expression of ISG20L2 has been found in several cancers and affected cancer occurrence in a variety of aspects ( Xu et al, 2020 ; Xiao et al, 2021 ). Nevertheless, there is scant literature with regard to its role in LUAD.…”

The expression profiles and prognostic values of HSP70s in hepatocellular carcinoma

“…Presently, 14 HSP70s members have been identified (HSPA1A, HSPA1B, HSPA1L, HSPA2, HSPA4, HSPA4L, HSPA5, HSPA6, HSPA8, HSPA9, HSPA12B, HSPA12A, HSPA13 and HSPA14). HSP70s have critical roles in tumor cells [ 10 , 11 ]. Some studies have found abnormal expression of some HSP70s and their prognostic value.…”

Establishment of a Novel Risk Score System of Immune Genes Associated With Prognosis in Esophageal Carcinoma

“…After blocking anti-PD-1, CD103+CD8 +TIL induced strong anti-tumor immunity (21). To help find individual immunotherapy targets, some recent studies established comprehensive prognostic indicators of lung squamous cell carcinoma, colorectal cancer and other tumors based on immune genome map analysis (22)(23)(24)(25)(26)(27)(28)(29). However, the prognostic value of immune-related genes in ESCC and EAC as two pathological sub-types of EC has not been fully elucidated.…”