ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Genetics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1519533
This article is part of the Research TopicExploring Epigenetic Mechanisms in CancerView all 10 articles
To explore the prognostic efficacy and mechanism of ABCC5 clinical scoring model in Hepatocellular carcinoma
Provisionally accepted
- 1Guangdong Provincial People's Hospital, Guangzhou, Guangdong Province, China
- 2YuanDong International Academy Of Life Sciences, Nanning, China
- 3Guangxi Academy of Sciences, Nanning, Guangxi Zhuang Region, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
AbstractObjective: The study found that ATP-binding cassette subfamily C member 5 (ABCC5) is highly expressed in hepatocellular carcinoma (HCC). It aims to explore ABCC5 role and prognostic value in HCC and uses the DrugBank database to identify potential therapeutic drugs targeting ABCC5, assessing its potential as a biomarker and treatment target for HCC.Methods: RNA-seq and clinical data from TCGA-LIHC and GSE76427 were analyzed to identify ABCC5-associated differentially expressed genes and miRNAs. Weighted gene co-expression network analysis revealed co-expression modules, and survival analysis assessed prognostic significance. Experimental validation included qRT-PCR, Western blot, migration assays, and drug response studies using the ABCC5 inhibitor zidovudine (ZDV).Result: ABCC5 was significantly overexpressed in HCC (p < 0.001) and correlated with poor overall (p = 0.008) and recurrence-free survival (p < 0.0001). WGCNA identified the MEturquoise module (enriched in cell cycle and p53 pathways) strongly linked to ABCC5 (r = 0.54). Immune infiltration analysis showed ABCC5 high-expression associated with Treg accumulation (immune suppression) and reduced mast cells. ZDV suppressed ABCC5 expression (~50%), activated p53 signaling (p53↑2.0-fold), and inhibited HCC migration and proliferation more effectively than the ABCC5-specific inhibitor MK-571. Somatic mutations (5% missense) and methylation (cg14480679, r = -0.43) further implicated ABCC5 in HCC progression. The ABCC5-based prognostic model, validated by calibration curves, independently predicted survival (p < 0.0001).Conclusion: This study constructed an ABCC5 clinical model and discovered that ABCC5 can serve as both a prognostic biomarker and therapeutic target for HCC. Multi-omics analysis and experimental validation confirmed that ABCC5 drives HCC progression by participating in immune microenvironment reprogramming, affecting cell cycle progression, and regulating the p53 signaling pathway. The research not only identified potential diagnostic markers and therapeutic targets, but the established prognostic model also provides new insights for investigating HCC pathogenesis and clinical translation.
Keywords: ABCC5, HCC, immune microenvironment, Multi-omics data, Drug Targets
Received: 30 Oct 2024; Accepted: 30 Jun 2025.
Copyright: © 2025 Deng, Yang, Huang, Long, Wu, Mo and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ke Mo, YuanDong International Academy Of Life Sciences, Nanning, China
Zijun Li, Guangxi Academy of Sciences, Nanning, Guangxi Zhuang Region, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.