P3H4 and PLOD1 expression associates with poor prognosis in bladder cancer

Clin Transl Oncol. 2022 Aug;24(8):1524-1532. doi: 10.1007/s12094-022-02791-1. Epub 2022 Feb 11.

Abstract

Purpose: The prolyl 3-hydroxylase family member 4 gene (P3H4) is involved in the development of human cancers. The association of P3H4 with bladder cancer (BC) prognosis is unclear. This study aimed to analyze the association of P3H4 with BC prognosis.

Methods: RNA-Seq data were downloaded from The Cancer Genome Atlas project and BC microarray datasets (GSE13507, GSE31684, and GSE32548) were downloaded from the Gene Expression Omnibus database. We analyzed the differences in P3H4 expression levels between BC tumors and non-tumor tissues and between samples with different clinical information. The association of P3H4 and P3H4-related genes with BC prognosis and the possibility of using P3H4 expression as a prognostic biomarker in BC patients were also analyzed. RevMan was used to perform the meta-analysis.

Results: P3H4 was upregulated in BC tissues compared with the adjacent non-tumor tissues (p = 4.06e-08). Univariate Cox regression analysis and meta-analysis showed that high P3H4 expression level contributed to a poor BC prognosis (Hazard ratio, HR = 1.348, 95% CI 1.140-1.594, p = 4.89e-04; meta-analysis: HR = 1.45, 95% CI 1.10-1.91; p = 9.00e-03). Among the genes related to P3H4, the PLOD1 gene was closely associated with P3H4 expression (r = 0.620, p = 2.49e-44). Also, a meta-analysis showed that PLOD1 expression was associated with a poor prognosis in BC patients (HR = 1.77, 95% CI 1.31-2.38; p = 2.00e-04).

Conclusions: The P3H4 and PLOD1 genes might be used as reliable prognostic biomarkers for BC.

Keywords: Bladder cancer; Meta-analysis; Microarray datasets; Overall survival; Prognostic biomarker.

Publication types

  • Meta-Analysis

MeSH terms

  • Autoantigens
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / genetics
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / metabolism
  • Prognosis
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Autoantigens
  • Biomarkers, Tumor
  • P3H4 protein, human
  • PLOD1 protein, human
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase