Pan-cancer analysis of IFN-γ with possible immunotherapeutic significance: a verification of single-cell sequencing and bulk omics research

Front Immunol. 2023 Aug 14:14:1202150. doi: 10.3389/fimmu.2023.1202150. eCollection 2023.

Abstract

Background: Interferon-gamma (IFN-γ), commonly referred to as type II interferon, is a crucial cytokine that coordinates the tumor immune process and has received considerable attention in tumor immunotherapy research. Previous studies have discussed the role and mechanisms associated with IFN-γ in specific tumors or diseases, but the relevant role of IFN-γ in pan-cancer remains uncertain.

Methods: TCGA and GTEx RNA expression data and clinical data were downloaded. Additionally, we analyzed the role of IFN-γ on tumors by using a bioinformatic approach, which included the analysis of the correlation between IFN-γ in different tumors and expression, prognosis, functional status, TMB, MSI, immune cell infiltration, and TIDE. We also developed a PPI network for topological analysis of the network, identifying hub genes as those having a degree greater than IFN-γ levels.

Result: IFN-γ was differentially expressed and predicted different survival statuses in a majority of tumor types in TCGA. Additionally, IFN-γ expression was strongly linked to factors like infiltration of T cells, immune checkpoints, immune-activating genes, immunosuppressive genes, chemokines, and chemokine receptors, as well as tumor purity, functional statuses, and prognostic value. Also, prognosis, CNV, and treatment response were all substantially correlated with IFN-γ-related gene expression. Particularly, the IFN-γ-related gene STAT1 exhibited the greatest percentage of SNVs and the largest percentage of SNPs in UCEC. Elevated expression levels of IFN-γ-related genes were found in a wide variety of tumor types, and this was shown to be positively linked to drug sensitivity for 20 different types of drugs.

Conclusion: IFN-γ is a good indicator of response to tumor immunotherapy and is likely to limit tumor progression, offering a novel approach for immunotherapy's future development.

Keywords: IFN-γ; immunotherapy; pan-cancer; single-cell transcriptome sequencing; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Cytokines
  • Humans
  • Immunotherapy
  • Interferon-gamma*
  • Neoplasms* / genetics
  • Neoplasms* / therapy

Substances

  • Interferon-gamma
  • Cytokines

Grants and funding

Guangxi Health Commission self-funded scientific research project (Z20200679) Guangxi Natural Science Foundation (2023GXNSFBA026070); Guangxi Health Commission self-funded scientific research project (Z-A20220031); Guangxi Natural Science Foundation (2022JJB140509) and Guangxi key research and development project (GuikeAB22080094); Guangxi Multidisciplinary Collaborative Health Management Talent Mini-Highland (guizutongzi:2019-85); Guangxi 14th Five-Year Major Science and Technology Special project (GuikeAA22096018) and Science and Technology Department Science and technology project (GuikeAD21220042).