Bulk and Single-Cell Transcriptional Profiles Reveal Roles of Fibroblasts and Immunocytes in Pan-Cancer Progression

Abstract

Tumors carry various dysregulated genes, of which many are found to be related to the overall survival of patients. These dysregulated genes are usually identified by bulk transcriptional comparison between tumors and their matching non-tumor tissues. However, because tumor tissues usually contain stromal cells in addition to cancer cells, it remains unclear whether the stromal cells within tumors also carry dysregulated genes. Here, to address this question, we combine bulk and single-cell gene expression data of tumor, adjacent and non-tumor tissues from 7 organs to explore the molecular and cellular mechanism of cancer progression. We found that fibroblasts within tumors across 7 cancer types commonly carry multiple dysregulated genes related to the overall survival of patients. Cell-cell communication analysis revealed significant interactions between cytotoxic immune cells and cancer fibroblasts through the PARs pathway, and self-activation of cancer associated fibroblasts (CAFs) via the PERIOSTIN pathway in pan-cancer. We also identified Colon cancer specific cycling B cells, which influence patients’ survival. Our study provides potential targets for pan-cancer therapy.