Cancer-associated fibroblast infiltration in gastric cancer: the discrepancy in subtypes pathways and immunosuppression

J Transl Med. 2021 Jul 31;19(1):325. doi: 10.1186/s12967-021-03012-z.

Abstract

Background: General role of cancer-associated fibroblast (CAF) and its infiltration characteristics in gastric cancer remains to be unknown.

Methods: We estimate CAF infiltration in bulk tumor tissue with RNA-seq data and analyzed its relationship with gastric cancer subtype, survival and immune microenvironment.

Results: We revealed CAF intend to have higher infiltration in diffuse, genomically stable, and advanced gastric cancer. CAF is associated with immunosuppressive microenvironment. Wide transcriptomics alterations occur in high CAF infiltrated gastric cancer, PI3K/AKT, TGFB and Hedgehog pathway are remarkable in this procedure. We utilized receptor tyrosine kinases and TGFB pathway ligands to construct risk score system that can predict survival.

Conclusion: Thus, CAF is associated with aggressive phenotype of gastric cancer and risk score based on RTK and TGFB pathway ligands expression is a promising tool for assessment of gastric cancer survival.

Keywords: Fibroblast; Gastric cancer; Immunosuppressive; Prognostic; Subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer-Associated Fibroblasts*
  • Hedgehog Proteins
  • Humans
  • Immunosuppression
  • Phosphatidylinositol 3-Kinases
  • Stomach Neoplasms* / genetics
  • Tumor Microenvironment

Substances

  • Hedgehog Proteins