Research Paper Volume 15, Issue 20 pp 11369—11388
Comprehensive analysis of integrin αvβ3/α6β1 in prognosis and immune escape of prostate cancer
- 1 Department of Urinary Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
Received: August 3, 2023 Accepted: October 2, 2023 Published: October 19, 2023
https://doi.org/10.18632/aging.205131How to Cite
Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Integrin αvβ3/α6β1 are crucial in the transduction of intercellular cancer information, while their roles in prostate cancer (PCa) remain poorly understood. Here, we systematically analyzed the transcriptome, single nucleotide polymorphisms (SNPs) and clinical data of 495 PCa patients from the TCGA database and verified them in 220 GEO patients, and qPCR was used to validate the expression of the model genes in our patients. First, we found that integrin αvβ3/α6β1 was negatively correlated with most immune cell infiltration and immune functions and closely associated with poor survival in TCGA patients. Then, we divided these patients into two groups according to the expression level of αvβ3/α6β1, intersected differentially expressed genes of the two groups with the GEO dataset and identified eight biochemical recurrence-related genes (BRGs), and these genes were verified by qPCR in our patients. Next, these BRGs were used to construct a prognostic risk model by applying LASSO Cox regression. We found that the high-risk (HR) group showed poorer OS, PFS, biochemical recurrence and clinical characteristics than the low-risk (LR) group. In addition, the HR group was mainly enriched in the cell cycle pathway and had a higher TP53 mutation rate than the LR group. More importantly, lower immune cell infiltration and immune function, higher expression of PD-L1, PD-1, and CTLA4, and higher immune exclusion scores were identified in the HR group, suggesting a higher possibility of immune escape. These findings suggested the key role of integrin αvβ3/α6β1 in predicting prognosis, TP53 mutation and immune escape in PCa.
Abbreviations
PCa: prostate cancer; SNPs: single nucleotide polymorphisms; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; HPA: Human Protein Atlas; LASSO: least absolute shrinkage and selection operator; HR group: high-risk group; LR group: low-risk group; AUC: Area under curve; ADT: androgen deprivation therapy; RT: radiation therapy; CRPC: castration-resistant prostate cancer; AR: Androgen receptor; ICIs: immune checkpoint inhibitors; APC: antigen presenting cells; TME: tumor microenvironment; TMB: tumor mutational burden; PPI: protein-protein interaction; DEGs: differentially expressed genes; GSEA: Gene set enrichment analysis; DAVID: Database for Annotation, Visualization and Integrated Discovery; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; ROC: Receiver operating characteristic; TILs: Tumor-infiltrating lymphocytes; PSA: Prostate-specific antigen; OS: Overall survival; RFS: Relapse-free survival; PFS: Progression-free survival; PCA: principal component analysis; t-SNE: t-distributed stochastic neighbor embedding; MTs: metallothioneins; BRGs: biochemical recurrence-related genes.