Prognostic values and immune suppression of the S100A family in pancreatic cancer

J Cell Mol Med. 2021 Mar;25(6):3006-3018. doi: 10.1111/jcmm.16343. Epub 2021 Feb 12.

Abstract

S100 calcium-binding protein A (S100A) family members regulate multiple biological functions related to pancreatic cancer (PC) progression and metastasis. However, the prognostic and oncologic values of S100A family have not been systematically investigated in PC. In the present study, the mRNA expression and potential functions of S100A family were investigated by bioinformatic analysis. Our results demonstrated that overexpression of S100A2, S100A6, S100A10, S100A11, S100A14 and S100A16 was significantly associated with higher T stage, advanced histologic grade and worse prognosis in PC. Besides, one CpG of S100A2, three CpG of S100A6, four CpG of S100A10, four CpG of S100A11, two CpG of S100A14 and five CpG of S100A16 were negatively associated with corresponding S100A family members expression and positively associated with overall survival (OS). The signature based on four CpGs showed good prediction ability of OS. Besides, S100A2 overexpression took part in the regulation of mitotic cell cycle, ECM-receptor interaction and HIF-1α transcription factor network. Overexpression of S100A6, S100A10, S100A11, S100A14 and S100A16 may impair the infiltration and cytolytic activity of CD8+ T cells through focal adhesion-Ras-stimulating signalling pathway in PC. Overall, this study explores the multiple prognostic values and oncologic functions of the S100A family in PC.

Keywords: CD8+ T cells; Ras-stimulating signalling pathway; S100A family; focal adhesion; pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor*
  • Computational Biology / methods
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunomodulation / genetics*
  • Kaplan-Meier Estimate
  • Multigene Family*
  • Neoplasm Grading
  • Neoplasm Staging
  • Pancreatic Neoplasms / etiology*
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Proportional Hazards Models
  • S100 Proteins / genetics*
  • S100 Proteins / metabolism
  • Signal Transduction
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • S100 Proteins