Spatial transcriptomics atlas reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment components in colorectal cancer

• DOI: 10.1186/s12967-022-03510-8
• Publication Date: 2022-07-06T09:02:58Z
• Authors: Zhiwei Peng; Manping Ye; Huiming Ding; Zhenyou Feng; Kongwang Hu
• Keywords: Cancer-Associated Fibroblasts; Crosstalk; Tumor progression

Abstract Background The tumor-promoting role of tumor microenvironment (TME) in colorectal cancer has been widely investigated biology. Cancer-associated fibroblasts (CAFs), as the main stromal component TME, play an important promoting progression and metastasis. Hence, we explored crosstalk between CAFs pathogenesis order to provide basis for precision therapy. Methods We integrated spatial transcriptomics (ST) bulk-RNA sequencing datasets explore functions CRC. In detail, single sample gene set enrichment analysis (ssGSEA), variation (GSVA), pseudotime cell proportion were utilized identify types each cluster. Immunofluorescence immunohistochemistry applied confirm results based on bioinformatics analysis. Results profiled heterogeneity landscape identified two distinct CAFs, which myo-cancer-associated (mCAFs) is associated with myofibroblast-like cells inflammatory-cancer-associated (iCAFs) related immune inflammation. When carried out functional uncovered extensive iCAFs components TME promote Noticeable, some anti-tumor such NK cells, monocytes significantly reduced iCAFs-enriched Then, ssGSEA showed that EMT, lipid metabolism bile acid etc. Besides, when relationship chemotherapy microenvironment, detected influenced immunosuppressive reprogramming patient who underwent chemotherapy. Additionally, clinical through a public database confirmed it poor prognosis. Conclusions summary, using data their significance TME. This in-depth understanding may help us elucidate its cancer-promoting offer hints therapeutic studies.