A paradoxical correlation of cancer-associated fibroblasts with survival outcomes in B-cell lymphomas and carcinomas

Marcela Haro, Sandra Orsulic

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The tumor microenvironment is increasingly recognized as an active participant in tumor progression. A recent pan-cancer genomic profile analysis has revealed that gene signatures representing components of the tumor microenvironment are robust predictors of survival. A stromal gene signature representing fibroblasts and extracellular matrix components has been associated with good survival in diffuse large B-cell lymphoma (DLBCL). Paradoxically, a closely related gene signature has been shown to correlate with poor survival in carcinomas, including breast, ovarian, pancreatic, and colorectal cancer. To date, there has been no explanation for this paradoxical inverse correlation with survival outcomes in DLBCL and carcinomas. Using public gene data sets, we confirm that the DLBCL stromal gene signature is associated with good survival in DLBCL and several other B-cell lymphomas while it is associated with poor survival in ovarian cancer and several other solid tumors. We show that the DLBCL stromal gene signature is enriched in lymphoid fibroblasts in normal lymph nodes and in cancer-associated fibroblasts (CAFs) in ovarian cancer. Based on these findings, we propose several possible mechanisms by which CAFs may contribute to opposite survival outcomes in B-cell lymphomas and carcinomas.

Original languageEnglish (US)
Article number98
JournalFrontiers in Cell and Developmental Biology
Volume6
Issue numberAUG
DOIs
StatePublished - Aug 28 2018
Externally publishedYes

Keywords

  • B cells
  • B-cell lymphoma
  • CAFs
  • Cancer-associated fibroblasts
  • DLBCL
  • Gene signature
  • Ovarian cancer
  • Tumor microenvironment

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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