Single-cell transcriptomics reveals tumor microenvironment changes and prognostic gene signatures in hepatocellular carcinoma.

Autor: Wu Y; School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai'an, China., Zhai Y; Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai Research Center of Biliary Tract Disease, Department of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China., Ding Z; Department of Hepatobiliary Surgery, The Affiliated Huaian Hospital of Xuzhou Medical University and Huai'an Second People's Hospital, Huai'an, Jiangsu, China., Xie T; School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai'an, China., Zhu W; School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai'an, China., Zhang C; School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai'an, China., Lu Y; School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai'an, China., Chen Y; School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai'an, China., Ren S; School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai'an, China., Hu Y; School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai'an, China., Li X; School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai'an, China., Zhong F; Department of Laboratory Medicine, The Affiliated Huaian Hospital of Xuzhou Medical University and Huai'an Second People's Hospital, Huai'an, Jiangsu, China. Electronic address: zf15252359695@163.com., Liang Y; Department of Laboratory Medicine, The Affiliated Huaian Hospital of Xuzhou Medical University and Huai'an Second People's Hospital, Huai'an, Jiangsu, China. Electronic address: zhongfei_email@163.com., Wang S; School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huai'an, China. Electronic address: wangshiyan1@gmail.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 25; Vol. 143 (Pt 2), pp. 113317. Date of Electronic Publication: 2024 Oct 23.
DOI: 10.1016/j.intimp.2024.113317
Abstrakt: Background: Hepatocellular Carcinoma (HCC) is the most common type of primary liver cancer, accounting for the majority of liver cancer cases. Hepatocellular Carcinoma not only exhibits high heterogeneity but also possesses an immune-suppressive tumor microenvironment that promotes tumor evasion, posing substantial difficulties for efficient therapy. Our aim is to utilize single-cell RNA transcriptome data to investigate the dynamic changes in the tumor microenvironment during the malignant progression of HCC, the communication among immune cells, and the marker genes associated with patient prognosis.
Methods: We constructed expression matrices from open single-cell RNA transcriptome data (GSE149614) of HCC patients (representing stages I-IV), establishing single-cell RNA transcriptional atlases for different stages of HCC progression. For each stage, we conducted cell subgroup analysis to identify cell types at each stage. Horizontally, we explored the dynamic changes of the same cell type across different stages, performing trajectory analysis and prognosis analysis. Vertically, we investigated pairwise comparisons of different stages of HCC progression, probing the dynamic alterations in tumor microenvironment immune cell signaling pathways. Finally, potential drugs for the treatment of HCC were predicted based on relevant genes.
Findings: As the HCC advances towards increased malignancy, there is a shift in the predominant composition of the tumor microenvironment, with a decline in the dominance of hepatic cells. Tumor-infiltrating immune cells migrate and accumulate within the tumor microenvironment, where T cells and myeloid cells display distinct patterns of change. Genes associated with cancer-associated fibroblasts (CAFs) and T cells are correlated with adverse patient outcomes. In the late stages of HCC, the tumor microenvironment is infiltrated by more myeloid-derived suppressor cells (MDSCs), and a prognostic model constructed based on genes related to myeloid cells can predict patient outcomes. Additionally, in the analysis of transcription factors, YY1 and MYC are found to be highly expressed. Cell communication analysis among tumor-infiltrating immune cells reveals significant differences in the main signaling pathways at different stages of HCC progression. Finally, drug sensitivity analysis based on key genes identifies Acetalax, Allopurinol, and Amonafide as potential candidates for HCC treatment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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