Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Key Lab of Digestive Organ Transplantation of Henan Province, Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou Key Laboratory of Hepatobiliary and Pancreatic Disease and Organ Transplantation, Zhengzhou, Henan 450052, P.R. China.
Biosci Rep. 2022 Feb 25;42(2). doi: 10.1042/BSR20212560.
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.
肝细胞癌 (HCC) 肿瘤表现出高度的异质性。然而，目前对于 HCC 肿瘤细胞异质性及其与预后的关联的理解仍然非常有限。在本研究中，我们通过单细胞 RNA 测序 (scRNA-seq) 收集并检测了一位 HCC 患者的肿瘤组织。我们鉴定了 5753 个细胞和 16 个簇，包括肝细胞/癌细胞、T 细胞、巨噬细胞、内皮细胞、成纤维细胞、NK 细胞、中性粒细胞和 B 细胞。在六个肿瘤细胞亚群中，我们鉴定出一个与不良预后相关的增殖性肿瘤细胞簇。我们从 NCBI-GEO 下载了 scRNA-seq 数据 GSE125449 作为验证数据集，发现 HCC 中存在一个具有高增殖活性的肝细胞簇。此外，我们鉴定出一个与 HCC 细胞增殖相关的基因特征。该基因特征可有效地将 HCC 患者分为 TCGA 和 ICGC 数据库队列中具有不同预后的两组。我们的研究结果揭示了 HCC 在单细胞水平的肿瘤内异质性，并鉴定出与 HCC 预后相关的基因特征。
