Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression

Gut Pathogens

Research

Wenbiao Chen¹  Yeda Chen¹  Peng Zhu²  Liangliang Yu³  Chenhong Lin³  Feng Zhang⁴ 

[1] Central Laboratory, People’s Hospital of Longhua, The Affiliated Hospital of Southern Medical University, 518109, Shenzhen, China;Central Laboratory, Shenzhen Pingshan District People’s Hospital, Pingshan General Hospital, Southern Medical University, 518110, Shenzhen, China;Department of Endoscopy Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310000, Hangzhou, China;Intensive Care Unit, The First Affiliated Hospital of Jinan University, 510000, Guangzhou, China;

关键词: HBV;    Cirrhosis;    HCC;    cancer-associated fibroblast;    PTN;    Single-cell RNA sequencing;   

DOI  :  10.1186/s13099-023-00554-z

 received in 2022-12-12, accepted in 2023-05-19,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCancer-associated fibroblasts (CAFs) are essential stromal components in the tumor microenvironment of hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) infection induces pathological changes such as liver fibrosis/cirrhosis and HCC. The aim of this research was to explore the novel mediators of CAFs to modulate HBV cirrhosis-HCC progression.MethodsThe single-cell transcriptome data of HCC were divided into subsets, and the significant subset related to fibrotic cells, along with biological function, and clinical information of HCC was revealed by integrated data analyses. The cell communication, cells communicated weight analysis of signaling pathways, and key genes in signaling pathways analysis of significant CAFs subclasses were conducted to discover the novel gene of CAFs. Bioinformatics, vitro and HBV transfection assays were used to verify the novel gene is an important target for promoting the progression HBV cirrhosis-HCC progression.ResultsFibroblasts derived from HCC single-cell data could be separated into three cell subclasses (CAF0-2), of which CAF2 was associated with the HCC clinical information. Fibroblasts have opposite developmental trajectories to immune B cells and CD8 + T cells. CAF0-2 had strong interaction with B cells and CD8 + T cells, especially CAF2 had the highest interaction frequency and weight with B cells and CD8 + T cells. Moreover, PTN participated in CAF2-related pathways involved in the regulation of cell communication, and the interactions among CAF2 and PTN contributed the most to B cells and CD8 + T cells. Furthermore, the genes of PTN, SDC1, and NCL from PTN signaling were highest expression in CAF2, B cells, and CD8 + T cells, respectively, and the interaction of PTN- SDC1 and PTN- NCL contributed most to the interaction of CAF2- B cells and CAF2-CD8 + T cells. Bioinformatics and vitro experiments confirm PTN was upregulated in HCC and promoted the proliferation of tumor cells, and HBV infection could initiate PTN to perform cirrhosis-HCC progression.ConclusionOur findings revealed CAF was associated with hepatocarcinogenesis, and the functional importance of B cells and CD8 + T cells in modulating CAF in HCC. Importantly, PTN maybe a novel mediator of CAF to mediate HBV cirrhosis-HCC progression.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 7

Fig. 2

13690_2023_1130_Article_IEq18.gif

Fig. 5

12302_2023_754_Article_IEq1.gif

40517_2023_252_Article_IEq122.gif

40517_2023_252_Article_IEq79.gif

Fig. 3

40517_2023_252_Article_IEq46.gif

40517_2023_252_Article_IEq39.gif

40517_2023_252_Article_IEq30.gif

Fig. 18

Fig. 3

Fig. 7