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

被引:8
作者
Lin, Chenhong [1 ]
Chen, Yeda [2 ]
Zhang, Feng [3 ]
Zhu, Peng [4 ]
Yu, Liangliang [1 ]
Chen, Wenbiao [2 ]
机构
[1] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Endoscopy Ctr, Hangzhou 310000, Peoples R China
[2] Southern Med Univ, Peoples Hosp Longhua, Affiliated Hosp, Cent Lab, Shenzhen 518109, Peoples R China
[3] Jinan Univ, Affiliated Hosp 1, Intens Care Unit, Guangzhou 510000, Peoples R China
[4] Southern Med Univ, Shenzhen Pingshan Dist Peoples Hosp, Pingshan Gen Hosp, Cent Lab, Shenzhen 518110, Peoples R China
基金
中国国家自然科学基金;
关键词
HBV; Cirrhosis; HCC; cancer-associated fibroblast; PTN; Single-cell RNA sequencing; HEPATOCELLULAR-CARCINOMA; PROMOTES PROLIFERATION; TUMOR MICROENVIRONMENT; PLEIOTROPHIN; LIVER; ANGIOGENESIS; METASTASIS; EXPRESSION; TARGET;
D O I
10.1186/s13099-023-00554-z
中图分类号
R57 [消化系及腹部疾病];
学科分类号
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.
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页数:15
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