A Prognostic Model Based on Adipokine-Related Genes for Hepatocellular Carcinoma: Assessment of Patient Outcomes and Tumor Microenvironment Characterization.

Authors

Jianwen Duan, Renya Jiang, Lei Yuan, Xiaofang Xu, Da Sun

Published in

Digestive diseases and sciences. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, and its marked heterogeneity is closely associated with the complex tumormicroenvironment. Adipokines are important mediators linking metabolic regulation and immune modulation; however, the prognostic value of adipokine-related genes (ARGs) andtheir association with drug sensitivity in HCC remain unclear.
Transcriptomic and clinical data for HCC were obtained from public databases. Diff erentially expressed ARGs were identifi ed, and a prognostic risk model was constructedusing univariate Cox regression, least absolute shrinkage and selection operator regression, and multivariate Cox regression, followed by validation in an independent cohort.Immune infi ltration, somatic mutation profi les, and predicted drug sensitivity were further analyzed. PGF was knocked down in Huh7 cells with or without imatinib treatment, andits functional eff ects were evaluated using CCK-8, colony formation, flow cytometry, gene set enrichment analysis, and western blotting.
A total of 113 diff erentially expressed ARGs were identifi ed, and a 10-gene prognostic signature was established. The model showed favorable predictive performance inthe TCGA cohort and retained survival stratifi cation ability in the external GEO cohort. Patients in the high-risk group had signifi cantly shorter overall survival and exhibited potentialdiff erences in immune microenvironment characteristics and mutation profi les. PGF expression was positively correlated with the predicted half-maximal inhibitory concentration of imatinib. Invitro experiments showed that PGF knockdown enhanced the inhibitory eff ects of imatinib on Huh7 cell proliferation and colony formation and promoted apoptosis. Further analysessuggested that these eff ects may involve the Pl3K/AKT and MAPK/ERK signaling pathways.
This study established an ARG-based prognostic model for HCC and preliminarily suggested that PGF may be involved in regulating the sensitivity of HCC cells toimatinib. These fi ndings provide a preliminary basis for further investigation of ARG-relaterognostic assessment and PGF-mediated drug sensitivity.

PMID:
42469546
Bibliographic data and abstract were imported from PubMed on 18 Jul 2026.

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