Single-Cell RNA-seq Analysis Reveals Dysregulated Cell-Cell Interactions in a Tumor Microenvironment Related to HCC Development

The heterogeneity of tumor microenvironment (TME) of hepatocellular carcinoma (HCC) may relate to cell-cell interaction event (CCE) dysregulation and would affect therapeutic responses and clinical outcomes. To reveal the differentiation of CCEs in the liver tissue from healthy donors (HD) to HCC, scRNA-seq data of ~62000 cells from HD, paracancerous nontumor tissue (NT), and HCC were analyzed. The microenvironmental CCE landscape was constructed. Dysregulated cell types and changed molecular functions were identified with CCE alterations in HCC. Dysregulated CCEs which function as pivotal roles in tumorigenesis and development of HCC included SPP1-CD44, MIF-TNFRSF14, and VEGFA-NRP1. A CCE-based immune regulatory network was extracted to illustrate the mechanism of TME dysregulation. A prognostic signature based on CCE genes was identified and validated in independent datasets. Our study provided insights into the characteristics of the cross-talk between tumor cells and microenvironment in HCC and established a workflow strategy for CCE analyses based on scRNA-seq data.

Automated summary

This study investigates the role of cell-cell interaction events (CCEs) in hepatocellular carcinoma (HCC) and its impact on therapeutic responses and clinical outcomes. By analyzing single-cell RNA sequencing data, the heterogeneity of tumor microenvironment (TME) and dysregulated CCEs in HCC were identified. Dysregulated CCEs such as SPP1-CD44, MIF-TNFRSF14, and VEGFA-NRP1 were found to play crucial roles in tumorigenesis and HCC development. The study also extracted a CCE-based immune regulatory network and identified a prognostic signature based on CCE genes. This research provides insights into the interaction between tumor cells and the microenvironment, and establishes a workflow strategy for CCE analyses based on scRNA-seq data.