Establishment of a prognostic model based on m6A regulatory factors and stemness of hepatocellular carcinoma using RNA-seq data and scRNA-seq data

Yan Liang; Sen Chen; Jinghe Xie; Guanrong Yan; Tingting Guo; Tianyang Li; Shoupei Liu; Weiping Zeng; Shuai Zhang; Keqiang Ma; Honglin Chen; Yimeng Ou; Bailin Wang; Weili Gu; Yuyou Duan

doi:10.1007/s00432-023-05045-x

Establishment of a prognostic model based on m⁶A regulatory factors and stemness of hepatocellular carcinoma using RNA-seq data and scRNA-seq data

J Cancer Res Clin Oncol. 2023 Nov;149(14):12881-12896. doi: 10.1007/s00432-023-05045-x. Epub 2023 Jul 19.

Authors

Yan Liang^#¹, Sen Chen^#^{1

2}, Jinghe Xie^#³, Guanrong Yan³, Tingting Guo^{1

2}, Tianyang Li⁴, Shoupei Liu^{1

2}, Weiping Zeng^{1

5}, Shuai Zhang⁴, Keqiang Ma⁶, Honglin Chen¹, Yimeng Ou⁷, Bailin Wang⁸, Weili Gu⁹, Yuyou Duan^{10

11

12

13}

Affiliations

¹ Laboratory of Stem Cells and Translational Medicine, School of Medicine, South China University of Technology, Guangzhou, 510006, People's Republic of China.
² Laboratory of Stem Cells and Translational Medicine, Institute for Medical Research, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
³ School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 510006, People's Republic of China.
⁴ Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, No.1 Panfu Road, Guangzhou, 510180, People's Republic of China.
⁵ School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510180, China.
⁶ Department of Hepatobiliary Pancreatic Surgery, Huadu District People's Hospital of Guangzhou, Guangzhou, 510800, People's Republic of China.
⁷ Department of General Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglin Xia Road, Guangzhou, 510699, People's Republic of China. yimengou@126.com.
⁸ Department of General Surgery, Guangzhou Red Cross Hospital, Jinan University, 601 Huangpu Dadao West Road, Guangzhou, 510220, People's Republic of China. wangbailin888@sina.com.
⁹ Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, No.1 Panfu Road, Guangzhou, 510180, People's Republic of China. lili-6423@163.com.
¹⁰ Laboratory of Stem Cells and Translational Medicine, School of Medicine, South China University of Technology, Guangzhou, 510006, People's Republic of China. yuyouduan@scut.edu.cn.
¹¹ Laboratory of Stem Cells and Translational Medicine, Institute for Medical Research, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China. yuyouduan@scut.edu.cn.
¹² National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510180, China. yuyouduan@scut.edu.cn.
¹³ Laboratory of Stem Cells and Translational Medicine, Institute for Clinical Medicine, The Second Affiliated Hospital, School of Medicine, South China University of Technology, No.1 Panfu Road, Guangzhou, 510180, People's Republic of China. yuyouduan@scut.edu.cn.

^# Contributed equally.

Abstract

Background: Hepatocellular carcinoma (HCC) with high incidence and mortality is one of the most common malignant cancers worldwide. Increasing evidence has reported that N6-methyladenosine (m⁶A) modification has been considered as a major contribution to the occurrence and development of tumors.

Method: In our study, we comprehensively analyzed the connection between m⁶A regulatory factors and cancer stem cells (CSCs) of HCC to establish a clinical tool for predicting its outcome. First, we concluded that the expression level of m⁶A regulatory factors was related with the stemness of hepatocellular carcinoma. Subsequently, we gained a ten hub regulatory factors that were associated with prognosis of hepatocellular carcinoma by overall survival (OS) analysis using ICGC and TCGA datasets, and these regulatory factors included YTHDF1, IGF2BP1, METTL3, IGF2BP3, HNRNPA2B1, IGF2BP2, RBM15B, HNRNPC, RBMX, and LRPPR. Next, we found that these ten hub m⁶A regulatory factors were highly expressed in CSCs, and CSCs related pathways were also enriched by the gene set variation analysis (GSVA). Then, correlation, consensus clustering and PCA analysis were performed to reveal potential therapeutic benefits of HCC. Moreover, univariate Cox regression (UNICOX), LASSON and multivariate Cox regression (MULTICOX) analyses were adopted to establish HCC prognosis prediction signature.

Results: Four regulatory factors RBM15B, LRPPRC, IGF2BP1, and IGF2BP3 were picked as valuable prognostic indicators.

Conclusion: In summary, these ten hub regulatory factors would be useful therapeutic targets for HCC treatment, and RBM15B/LRPPRC/IGF2BP1/IGF2BP3 prognostic indicators can be used to guide therapy for HCC patients.

Keywords: CSCs; HCC; Prognostic model; Stemness; m6A modification.

Abstract

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