Single-cell transcriptomics analysis reveals intratumoral heterogeneity and identifies a gene signature associated with prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) tumors exhibit high heterogeneity. However, current understanding of tumor cell heterogeneity of HCC and the association with prognosis remains very limited. In the present study, we collected and examined tumor tissue from one HCC patient by single-cell RNA sequencing (scRNA-seq). We identified 5753 cells and 16 clusters including hepatocytes/cancer cells, T cells, macrophages, endothelial cells, fibroblasts, NK cells, neutrophils, and B cells. In six tumor cell subclusters, we identified a cluster of proliferative tumor cells associated with poor prognosis. We downloaded scRNA-seq data of GSE125449 from the NCBI-GEO as validation dataset, and found that a cluster of hepatocytes exhibited high proliferation activity in HCC. Furthermore, we identified a gene signature related to the proliferation of HCC cells. This gene signature is efficient to classify HCC patients into two groups with distinct prognosis in both TCGA and ICGC database cohorts. Our results reveal the intratumoral heterogeneity of HCC at single cell level and identify a gene signature associated with HCC prognosis.