Comprehensive analysis of integrin αvβ3/α6β1 in prognosis and immune escape of prostate cancer

Aging (Albany NY). 2023 Oct 19;15(20):11369-11388. doi: 10.18632/aging.205131. Epub 2023 Oct 19.

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.

Keywords: immune escape; integrin αvβ3/α6β1; prognosis; prostate cancer; risk model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Databases, Factual
  • Humans
  • Integrin alphaVbeta3*
  • Male
  • Prognosis
  • Prostatic Neoplasms* / genetics

Substances

  • Integrin alphaVbeta3