Bioinformatics Analysis of GFAP as a Potential Key Regulator in Different Immune Phenotypes of Prostate Cancer

Abstract

Tumor immune escape plays an essential role in both cancer progression and immunotherapy responses. For prostate cancer (PC), however, the molecular mechanisms that drive its different immune phenotypes have yet to be fully elucidated. Patient gene expression data were analyzed from The Cancer Genome Atlas-prostate adenocarcinoma (TCGA-PRAD) and the International Cancer Genome Consortium (ICGC) databases. We used a Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis and an unsupervised clustering analysis to identify patient subgroups with distinct immune phenotypes. These distinct phenotypes were then explored for associations for differentially expressed genes (DEGs) and both epigenetic and genetic landscapes. Finally, we used a protein-protein interaction analysis to identify key hub genes. We identified two patient subgroups with independent immune phenotypes associated with the expression of Programmed death-ligand 1 (PD-L1). Patient samples in Cluster 1 ( C 1 ) had higher scores for immune-cell subsets compared to Cluster 2 ( C 2 ), and C 2 samples had higher specific somatic mutations, MHC mutations, and genomic copy number variations compared to C 1 . We also found additional cluster phenotype differences for DNA methylation, microRNA (miRNA) expression, and long noncoding RNA (lncRNA) expression. Furthermore, we established a 4-gene model to distinguish between clusters by integrating analyses for DEGs, lncRNAs, miRNAs, and methylation. Notably, we found that glial fibrillary acidic protein (GFAP) might serve as a key hub gene within the genetic and epigenetic regulatory networks. These results improve our understanding of the molecular mechanisms underlying tumor immune phenotypes that are associated with tumor immune escape. In addition, GFAP may be a potential biomarker for both PC diagnosis and prognosis.

Tissue-specific biological aging predicts progression in prostate cancer and acute myeloid leukemia

“…GFAP is a glial fibrillary acidic protein that is a promising biomarker and therapeutic target in glioblastoma ( 69 ) and other cancers ( 70 , 71 ); however, its role in prostate cancer has not been fully explored. One of the bioinformatics investigations nominated GFAP as a potential regulator of immune phenotypes in prostate cancer ( 72 ), yet its role in prostate cancer progression provides a new exciting avenue for further investigation, especially in combination with GADD45B, STAT3, and GFAP (and, potentially, FOXM1).…”

Tau, Glial Fibrillary Acidic Protein, and Neurofilament Light Chain as Brain Protein Biomarkers in Cerebrospinal Fluid and Blood for Diagnosis of Neurobiological Diseases

“…GFAP serves as a biomarker for tumor progression and treatment response in various brain cancers, including astrocytomas, glioblastomas, ependymomas, and metastases [ 79 , 80 , 81 , 82 ]. GFAP is a well-known marker of astrocytoma.…”