Comprehensive analysis reveals that P4HA3 is a prognostic and diagnostic gastric cancer biomarker that can predict immunotherapy efficacy

Sci Rep. 2024 Oct 3;14(1):22959. doi: 10.1038/s41598-024-73784-z.

Abstract

Gastric cancer (GC) is one of the most challenging malignant tumors worldwide, primarily because of its high incidence and mortality rates. Prolyl 4-hydroxylase subunit alpha 3 (P4HA3) has been established as a pivotal factor for facilitating cell proliferation, invasion, and metastasis across multiple human tumors. Nevertheless, the precise role of P4HA3in GC has not been fully elucidated. In this study, we used data from The Cancer Genome Atlas (TCGA) to examine the role of P4HA3 as a potential biomarker for predicting immunotherapy response in patients with GC. Our comprehensive analysis of data from the TCGA, TIMER, and other databases revealed a significant association between elevated P4HA3 expression in GC and adverse prognostic outcomes. Furthermore, we confirmed that P4HA3 expression was strongly correlated with immune infiltrating cells, immune infiltration markers, the tumor mutational burden (TMB), microsatellite instability (MSI), the immune score, the stromal score, and immune checkpoints, thus highlighting P4HA3 as a crucial and dependable therapeutic target within the context of immune-based antitumor strategies. Our findings suggest that P4HA3 may function as an immune-related biomarker in the pathogenesis and treatment of GC, indicating that P4HA3 is a promising prognostic and therapeutic target for this malignancy.

Keywords: Gastric cancer; Immunotherapy; P4HA3; Prognostic.

MeSH terms

  • Biomarkers, Tumor* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunotherapy* / methods
  • Male
  • Microsatellite Instability
  • Mutation
  • Procollagen-Proline Dioxygenase / genetics
  • Procollagen-Proline Dioxygenase / metabolism
  • Prognosis
  • Stomach Neoplasms* / diagnosis
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / immunology
  • Stomach Neoplasms* / mortality
  • Stomach Neoplasms* / pathology
  • Stomach Neoplasms* / therapy

Substances

  • Biomarkers, Tumor
  • Procollagen-Proline Dioxygenase
  • P4HA3 protein, human