Telomere-methylation genes: Novel prognostic biomarkers for hepatocellular carcinoma

Jia-Wen Xie; Hui-Ling Wang; Ling-Qing Lin; Yin-Feng Guo; Mao Wang; Xiao-Zhen Zhu; Jian-Jun Niu; Li-Rong Lin

doi:10.1016/j.clinre.2024.102516

Telomere-methylation genes: Novel prognostic biomarkers for hepatocellular carcinoma

Clin Res Hepatol Gastroenterol. 2024 Dec 14;49(1):102516. doi: 10.1016/j.clinre.2024.102516. Online ahead of print.

Authors

Jia-Wen Xie¹, Hui-Ling Wang², Ling-Qing Lin³, Yin-Feng Guo¹, Mao Wang⁴, Xiao-Zhen Zhu⁵, Jian-Jun Niu⁶, Li-Rong Lin⁷

Affiliations

¹ Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China.
² Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
³ Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China.
⁴ Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China; Department of Pathology, Chengdu Wenjiang District People's Hospital, Chengdu, China.
⁵ Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China. Electronic address: zhuxiaozhen@xmu.edu.cn.
⁶ Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China. Electronic address: niujianjun211@xmu.edu.cn.
⁷ Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China. Electronic address: linlirong@xmu.edu.cn.

PMID: 39675625
DOI: 10.1016/j.clinre.2024.102516

Abstract

Background: Since telomere length and DNA methylation both correlate with hepatocellular carcinoma (HCC) prognosis, telomere-methylation genes could be novel prognostic markers for HCC.

Method: This study first investigated the interaction between telomere length and DNA methylation in HCC through Mendelian randomization analysis. Then, this study identified telomere-methylation genes in HCC by employing the TCGA-LIHC cohort, and explored the expression patterns of these genes in the tumor microenvironment of HCC and potential underlying mechanisms. Finally, the HCC risk-scoring model and prognostic model based on these genes were established, and the performance of the model was assessed.

Result: The findings revealed a bidirectional relationship between telomere length and DNA methylation in HCC. Fifty telomere-methylation genes were identified, and the prognosis-related telomere-methylation genes were closely associated with Treg and Tprolif cell subsets within the HCC tumor microenvironment. Telomere-methylation genes could potentially impact the prognosis of HCC patients by modulating chromosome stability and regulating the cell cycle. Additionally, the constructed risk scoring model and prognostic prediction model showcased compelling clinical applicability, as evidenced by the receiver operating characteristic curve, the decision curve analysis, and the calibration curves.

Conclusion: This study elucidated the potential of telomere-methylation genes as prognostic biomarkers for HCC and paves the way for novel approaches in prognostication and treatment management for HCC patients.

Keywords: DNA methylation; Hepatocellular carcinoma; Prognosis; Prognosis biomarkers; Telomere.