A novel four-gene signature predicts immunotherapy response of patients with different cancers

J Clin Lab Anal. 2022 Jul;36(7):e24494. doi: 10.1002/jcla.24494. Epub 2022 May 19.

Abstract

Background: Immune checkpoint blockade (ICB) therapy has demonstrated favorable clinical efficacy, particularly for advanced or difficult-to-treat cancer types. However, this therapy is ineffective for many patients displaying lack of immune response or resistance to ICB. This study aimed to establish a novel four-gene signature (CD8A, CD8B, TCF7, and LEF1) to provide a prognostic immunotherapy biomarker for different cancers.

Methods: Transcriptome profiles and clinical data were obtained from The Cancer Genome Atlas database. Multivariate Cox regression analysis was used to establish a four-gene signature. The R package estimate was used to obtain the immune score for every patient.

Results: Risk scores of the novel four-gene signature could effectively divided all patients into high- and low-risk groups, with distinct outcomes. The immune score calculated via the estimate package demonstrated that the four-gene signature was significantly associated with the immune infiltration level. Furthermore, the four-gene signature could predict the response to atezolizumab immunotherapy in patients with metastatic urothelial cancer.

Conclusions: The novel four-gene signature developed in this study is a good prognostic biomarker, as it could identify many kinds of patients with cancer who are likely to respond to and benefit from immunotherapy.

Keywords: CD8; LEF1; TCF7; cancer; immune checkpoint-blockade.

MeSH terms

  • Biomarkers, Tumor* / genetics
  • Humans
  • Immunologic Factors
  • Immunotherapy
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Prognosis
  • Transcriptome / genetics

Substances

  • Biomarkers, Tumor
  • Immunologic Factors