Integrative Analyses of Bulk and Single-cell Transcriptomics Reveals The Infiltration and Crosstalk of Cancer-Associated Fibroblasts As a Novel Predictor for Prognosis and Microenvironment Remodeling in Intrahepatic Cholangiocarcinoma

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood. Methods To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts(CAFs) inflitration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue. Results EVA1A, APBA2, LRRTM4, GOLGA8M and BPIFB2 were identified as candidate CAFs-infiltration biomarker in Intrahepatic cholangiocarcinoma. The risk model derived from these markers displayed satisfactory performance. Additionally, our study also depicted the cell communication atlas between fibroblast and other cells. Especially, the signal transduction from fibroblasts to malignant cells via different pathways obviously enhanced, which subsequently trigger cascade activation of their downstream signaling pathways in tumor cells, such as PI3K-AKT and Notch pathways, regulating epithelial-mesenchymal transformation and invasion. Conclusions This study reveals the close association between fibroblasts infiltration and poor prognosis of intrahepatic cholangiocarcinoma. Enhanced intercellular transduction from fibroblasts to other cells and activated abnormal signaling pathways in tumor may give rise to microenvironment remodeling and tumor progression.