The Impact of Cancer-Associated Fibroblasts on the Biology and Progression of Colorectal Carcinomas.
Larissa Maria HenrichKristina GreimelmaierMichael WessollyNick Alexander KloppElena MairingerYvonne KrauseSophia BergerJeremias WohlschlaegerHans-Ulrich SchildhausHideo Andreas BabaFabian Dominik MairingerSabrina BorchertPublished in: Genes (2024)
(1) Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. Cancer-associated fibroblasts (CAFs) are major components of CRC's tumour microenvironment (TME), but their biological background and interplay with the TME remain poorly understood. This study investigates CAF biology and its impact on CRC progression. (2) The cohort comprises 155 cases, including CRC, with diverse localizations, adenomas, inflammations, and controls. Digital gene expression analysis examines genes associated with signalling pathways (MAPK, PI3K/Akt, TGF-β, WNT, p53), while next-generation sequencing (NGS) determines CRC mutational profiles. Immunohistochemical FAP scoring assesses CAF density and activity. (3) FAP expression is found in 81 of 150 samples, prevalent in CRC (98.4%), adenomas (27.5%), and inflammatory disease (38.9%). Several key genes show significant associations with FAP-positive fibroblasts. Gene set enrichment analysis (GSEA) highlights PI3K and MAPK pathway enrichment alongside the activation of immune response pathways like natural killer (NK)-cell-mediated cytotoxicity via CAFs. (4) The findings suggest an interplay between CAFs and cancer cells, influencing growth, invasiveness, angiogenesis, and immunogenicity. Notably, TGF-β, CDKs, and the Wnt pathway are affected. In conclusion, CAFs play a significant role in CRC and impact the TME throughout development.
Keyphrases
- pi k akt
- signaling pathway
- cell proliferation
- immune response
- genome wide identification
- stem cells
- copy number
- genome wide
- oxidative stress
- nk cells
- cell cycle arrest
- extracellular matrix
- transforming growth factor
- endothelial cells
- binding protein
- toll like receptor
- vascular endothelial growth factor
- genome wide analysis
- wound healing