Telomere-Methylation Genes: Novel Prognostic Biomarkers for Hepatocellular Carcinoma - 14/12/24

Doi : 10.1016/j.clinre.2024.102516

Jia-Wen Xie ^a,^b,^{^{#
These authors have contributed equally to this work and share first authorship}}, Hui-Ling Wang ^c,^{^{#
These authors have contributed equally to this work and share first authorship}}, Ling-Qing Lin ^a,^{^{#
These authors have contributed equally to this work and share first authorship}}, Yin-Feng Guo ^a,^b, Mao Wang ^a,^b,^d, Xiao-Zhen Zhu ^a,^b,^⁎ , Jian-Jun Niu ^a,^b,^⁎ , Li-Rong Lin ^a,^b,^⁎
^a Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China
^b Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China
^c Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China
^d Department of Pathology, Chengdu Wenjiang District People's Hospital, Chengdu, China

^⁎Corresponding authors. Centre of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, 361004, ChinaCentre of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen UniversityXiamen361004China

Sous presse. Manuscrit accepté. Disponible en ligne depuis le Saturday 14 December 2024

Highlights

•	A bidirectional link between telomere length and DNA methylation exists in HCC.
•	Telomere-methylation genes can be an innovative prognostic biomarker for HCC.
•	This study provided novel methods for prognosis and treatment for HCC patients.

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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.

Le texte complet de cet article est disponible en PDF.