Risk subtyping and prognostic assessment of prostate cancer based on consensus genes

Commun Biol. 2022 Mar 15;5(1):233. doi: 10.1038/s42003-022-03164-8.

Abstract

Prostate cancer (PCa) is the most frequent malignancy in male urogenital system around worldwide. We performed molecular subtyping and prognostic assessment based on consensus genes in patients with PCa. Five cohorts containing 1,046 PCa patients with RNA expression profiles and recorded clinical follow-up information were included. Univariate, multivariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression were used to select prognostic genes and establish the signature. Immunohistochemistry staining, cell proliferation, migration and invasion assays were used to assess the biological functions of key genes. Thirty-nine intersecting consensus prognostic genes from five independent cohorts were identified. Subsequently, an eleven-consensus-gene classifier was established. In addition, multivariate Cox regression analyses showed that the classifier served as an independent indicator of recurrence-free survival in three of the five cohorts. Combined receiver operating characteristic (ROC) analysis achieved synthesized effects by combining the classifier with clinicopathological features in four of five cohorts. SRD5A2 inhibits cell proliferation, while ITGA11 promotes cell migration and invasion, possibly through the PI3K/AKT signaling pathway. To conclude, we established and validated an eleven-consensus-gene classifier, which may add prognostic value to the currently available staging system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism
  • Consensus
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Membrane Proteins / metabolism
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Prognosis
  • Prostatic Neoplasms* / diagnosis
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism

Substances

  • Membrane Proteins
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • SRD5A2 protein, human