An integrated bioinformatic investigation of focal adhesion-related genes in glioma followed by preliminary validation of COL1A2 in tumorigenesis

Aging (Albany NY). 2023 Jun 22;15(13):6225-6254. doi: 10.18632/aging.204834. Epub 2023 Jun 22.

Abstract

Focal adhesions (FAs) allow cells to contact the extracellular matrix, helping to maintain tension and enabling signal transmission in cell migration, differentiation, and apoptosis. In addition, FAs are associated with changes in the tumor microenvironment (TME) that lead to malignant progression and drug resistance in tumors. However, there are still few studies on the comprehensive analysis of focal adhesion-related genes (FARGs) in glioma. Expression data and clinical information of glioma samples were downloaded from public databases. Two distinct molecular subtypes were identified based on FARGs using an unsupervised consensus clustering algorithm. A scoring system consisting of nine FARGs was constructed using integrated LASSO regression and multivariate Cox regression. It not only has outstanding prognostic value but also can guide immunotherapy of glioma patients, which was verified in TCGA, CGGA, GSE16011, and IMvigor210 cohorts. The results of bioinformatics analysis, immunohistochemistry staining, and western blotting all revealed that the expression of COL1A2 was up-regulated in glioblastoma and related to poor prognosis outcomes in patients from public datasets. COL1A2 promotes the proliferation, migration, and invasion of glioblastoma cells. A positive correlation between COL1A2 and CD8 was determined in GBM specimens from eight patients. Moreover, the results of cell co-cultured assay showed that COL1A2 participated in the killing of GBM cells by Jurkat cells. Our study indicates that the FARGs have prominent application value in the identification of molecular subtypes and prediction of survival outcomes in glioma patients. Bioinformatics analysis and experimental verification provide a direction for further research on FARGs.

Keywords: focal adhesion-related genes; immune checkpoint; immunotherapy; prognosis; tumor microenvironment.

MeSH terms

  • Carcinogenesis
  • Cell Transformation, Neoplastic
  • Collagen Type I
  • Focal Adhesions
  • Glioblastoma*
  • Glioma* / genetics
  • Humans
  • Prognosis
  • Tumor Microenvironment / genetics

Substances

  • Collagen Type I, alpha2 Subunit
  • COL1A2 protein, human
  • Collagen Type I