Evidence map›Paper›PMID 42104475›Full record

ArticleClinical epigenetics2026

Prognostic value of PRAME gene promoter methylation and expression in hepatocellular carcinoma.

Jintao Zheng, Guoqiang Cao, Jialing Zhao, Longjie Yu, Xiujin Ye, Junru Chen, Haiyang Xie, Jianhui Li, Changku Jia

Abstract read
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Article in Clinical epigenetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Jintao ZhengThe Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou First People's Hospital, Hangzhou, 310053, Zhejiang, China.
Guoqiang CaoNHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang, China.
Jialing ZhaoDepartment of Hepatopancreatobiliary Surgery, Hangzhou First People's Hospital, Hangzhou, 310006, Zhejiang, China.
Longjie YuDepartment of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, 310004, Zhejiang, China.
Xiujin YeDepartment of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.
Junru ChenDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
Haiyang XieNHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang, China.
Jianhui LiDepartment of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, 310004, Zhejiang, China. surgeonlee@126.com.
Changku JiaDepartment of Hepatopancreatobiliary Surgery, Hangzhou First People's Hospital, Hangzhou, 310006, Zhejiang, China. jiachk@126.com.

Funding

National Natural Science Foundation of China 82203240The High-level Talent Promotion and Training Project of Kunming 2022SCP002Zhejiang Provincial Natural Science Foundation of China LTGY24H160024
6 · The paper itself

Abstract

backgroundPRAME is a member of the cancer-testis antigen family and exhibits abnormally high expression in various solid tumors. Epigenetic regulation plays a critical role in the development and progression of hepatocellular carcinoma (HCC). Alterations in promoter methylation of specific genes have been widely recognized as valuable biomarkers for predicting cancer risk and assessing prognosis.

objectiveThis study systematically investigated the biological function and clinical relevance of PRAME promoter methylation in HCC.

methodsUsing data from The Cancer Genome Atlas (TCGA) cohort, we identified methylation-associated prognostic genes and examined the association between PRAME promoter methylation, its mRNA expression levels, overall survival (OS), and clinicopathologic characteristics. We then validated these findings in an independent HCC cohort from Shulan (Hangzhou) Hospital using MethylTarget multiplex gene methylation detection technology. To investigate the potential role of PRAME in vascular invasion and metastasis, we conducted Gene Ontology (GO) enrichment analysis and Gene Set Enrichment Analysis (GSEA) at both histological and cellular levels.

resultsAnalyses across three HCC cohorts consistently showed that the PRAME promoter is generally hypomethylated in tumor tissues, and this hypomethylation was significantly correlated with elevated PRAME mRNA expression. In both the TCGA and Shulan (Hangzhou) Hospital cohorts, PRAME promoter hypomethylation was associated with more advanced clinicopathologic features and shorter OS. Moreover, PRAME promoter methylation status was strongly linked to vascular invasion and distant metastasis in HCC. Further functional analyses revealed significant upregulation of Wnt signaling and cell adhesion-related pathways in tissues with high PRAME expression, a finding corroborated by single-cell RNA sequencing data.

conclusionHypomethylation of the PRAME promoter is closely associated with poor overall survival, adverse clinicopathologic features, vascular invasion, and metastasis in HCC patients. It plays a pivotal role in regulating gene expression and promoting tumor invasiveness. These findings suggest that PRAME promoter methylation may serve as a promising epigenetic biomarker for prognostic evaluation in HCC.

Indexed as

Antigens, NeoplasmCarcinoma, HepatocellularDNA MethylationLiver NeoplasmsBiomarkers, TumorEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedPrognosisPromoter Regions, GeneticAntigens, NeoplasmBiomarkers, TumorPRAME protein, humanCell adhesionEpigenetic biomarkerHepatocellular carcinomaPRAME

Identifiers

PMID42104475
PMCPMC13195865

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