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Original Article | Open Access

Single-cell transcriptome analysis reveals a cancer-associated fibroblast marker gene signature in hepatocellular carcinoma that predicts prognosis

Hao Chia,1, Dapeng Chena,1, Yuliang Zhanga,1, Zilin Cuib, Yi Baib, Yamin Zhangb( )
Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300192, China
Department of Hepatobiliary Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China

1 These authors contributed equally to this work.

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Abstract

Background and aims

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death. Multi-pathway combination therapy is used to treat HCC, and immunotherapy is also a routine part of treatment. As a major component of the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) actively participate in cancer progression through complex functions. However, because CAFs dynamically change during cancer development, most of the current treatment strategies targeting CAFs fail. We created a prognostic CAF marker gene signature (CAFMGS) to investigate the utility of CAFs as a prognostic factor and therapeutic target.

Methods

Gene Expression Omnibus (GEO) single-cell RNA sequencing (Sc-RNA-seq) data were analyzed to identify CAF marker genes in HCC. The Cancer Genome Atlas (TCGA) database was used as a training cohort to construct the CAFMGS model and the International Cancer Genome Consortium (ICGC) dataset was used to validate the CAFMGS.

Results

Marker genes in the CAFMGS model were (0.0001-SPP1), (0.0084-VCX3A), (0.0015-HMGA1), (0.0082-PLOD2), and (0.0075-CACYBP). The CAFMGS_score was separated into high-risk and low-risk groups based on the median of the patients' OS. Univariate and multivariate analyses confirmed that CAFMGS_score was an independent prognostic factor in the training group. CAFMGS_score was a more accurate prognostic indicator compared with clinicopathological score and tumor mutational burden score.

Conclusion

CAFMGS offers a fresh perspective on stromal cell marker genes in HCC prognosis and expands our knowledge of CAF heterogeneity and functional diversity, perhaps paving the way for CAF-targeted immunotherapy in HCC patients.

Keywords

Hepatocellular carcinomaCancer-associated fibroblast marker genesPrognostic signature

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iLIVER
Volume 2 Issue 1,
March 2023
Pages 16-25
DOI: 10.1016/j.iliver.2022.12.002
Cite this article:
Chi H, Chen D, Zhang Y, et al. Single-cell transcriptome analysis reveals a cancer-associated fibroblast marker gene signature in hepatocellular carcinoma that predicts prognosis. iLIVER, 2023, 2(1): 16-25. https://doi.org/10.1016/j.iliver.2022.12.002

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Received: 06 September 2022
Revised: 12 December 2022
Accepted: 14 December 2022
Published: 13 January 2023
© 2023 The Author(s). Published by Elsevier Ltd on behalf of Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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