Establishment and validation of a novel integrin-based prognostic gene signature that sub-classifies gliomas and effectively predicts immunosuppressive microenvironment

Cell Cycle. 2023 May;22(10):1259-1283. doi: 10.1080/15384101.2023.2205204. Epub 2023 Apr 25.

Abstract

The integrin family members play a key role in cancer immunomodulation and prognosis. We comprehensively analyzed the expression patterns and clinical significance of integrin family-related genes in gliomas. A total of 2293 gliomas from the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and Gliovis platform were enrolled for analyses. Twenty-six integrin coding genes showed different expression patterns between glioma and normal brain tissues. We screened an integrin family-related gene signature (ITGA5, ITGA9, ITGAE, ITGB7 and ITGB8) that showed independent prognostic value and sub-classified gliomas into different prognostic and molecular clusters, further composed an integrin-based risk score model associated with glioma malignant clinical features, overall survival (OS), and immune microenvironment alterations. Besides, glioma patients with high-risk scores showed chemotherapeutic resistance and more immune cells infiltration as well as high immune checkpoints expression. Concurrently, we also revealed that high-risk score group presented resistance to T cell-mediated cancer killing process and lower rates of response to immune checkpoint blockade (ICB) treatment. In conclusion, our study identified a valuable integrin gene signature that predicted gliomas OS effectively, and sub-classified them into different phenotypes and accompanied with immunological changes, possibly acted as a biomarker for ICB treatment.

Keywords: Glioma; immune microenvironment; integrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Clinical Relevance
  • Glioma* / genetics
  • Humans
  • Integrins / genetics
  • Prognosis
  • Tumor Microenvironment / genetics

Substances

  • Integrins

Grants and funding

This study was funded by the Liaoning Province Special Professor Project (No. 3110517003)