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World J Gastrointest Oncol. Nov 15, 2026; 18(11): 124061
Published online Nov 15, 2026. doi: 10.4251/wjgo.124061
Published online Nov 15, 2026. doi: 10.4251/wjgo.124061
Ferroptosis-mitochondria-related molecular subtypes and prognostic signature reveal immune and pathway heterogeneity in hepatocellular carcinoma
Shan Han, Yun Ran, Jin-Zhen Lv, Xiao-Bin Li, Cong-Hui Wang, Long-Zhu Wang, Shi-Ping Hu, Department of Hepatology, Beijing University of Chinese Medicine Shenzhen Hospital (Longgang), Shenzhen 518172, Guangdong Province, China
Zhi-Wei Feng, Department of Encephalopathy, Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing 100029, China
Gui-Ping Ma, Central Laboratory, Beijing University of Chinese Medicine Shenzhen Hospital (Longgang), Shenzhen 518172, Guangdong Province, China
Yi-Chi Zhou, Department of Spleen and Stomach Diseases, Beijing University of Chinese Medicine Shenzhen Hospital (Longgang), Shenzhen 518172, Guangdong Province, China
Co-first authors: Shan Han and Zhi-Wei Feng.
Author contributions: Han S and Feng ZW contributed equally to this work as co-first authors; Han S was responsible for conceptualization, data curation, formal analysis, visualization, and preparation of the original draft; Feng ZW performed data acquisition, bioinformatics analysis, software implementation, validation, and figure preparation; Ran Y contributed to methodology and data interpretation; Ma GP performed the biostatistical review of the statistical design, analytical procedures, reported outputs, and statistical interpretation; Zhou YC, Lv JZ, and Li XB contributed to results verification; Wang CH and Wang LZ contributed to data validation and result interpretation; Ran Y, Ma GP, Zhou YC, Lv JZ, Li XB, Wang CH, and Wang LZ contributed to manuscript revision; Zhou YC, Lv JZ, Li XB, Wang CH, and Wang LZ contributed to literature review; Hu SP was responsible for conceptualization, supervision, project administration, funding acquisition, critical manuscript revision, and final approval of the submitted version. All authors read and approved the final manuscript.
AI contribution statement: No artificial intelligence tools were used in this manuscript.
Supported by General Program of the Guangdong Basic and Applied Basic Research Foundation, No. 2025A1515011796; Guangdong Provincial Enterprise Joint Fund, No. 2023A1515220096; General Program of the Shenzhen Natural Science Foundation, No. JCYJ20240813165129038; Open Project of the National Key Laboratory for Integration and Innovation of Classical Formulas and Modern Chinese Medicine, No. LSLSKL20240117; and Sanming Project of Medicine in Shenzhen, No. SZZYSM202311018.
Institutional review board statement: This study used only publicly available, de-identified datasets and involved no new human participants or clinical specimens; therefore, additional institutional review board approval was not required.
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets analyzed in this study are publicly available from The Cancer Genome Atlas, Gene Expression Omnibus, International Cancer Genome Consortium, FerrDb, MitoCarta 3.0, and UALCAN-CPTAC. Processed data and statistical code are available from the corresponding author upon reasonable request.
Corresponding author: Shi-Ping Hu, PhD, Chief Physician, Full Professor, Department of Hepatology, Beijing University of Chinese Medicine Shenzhen Hospital (Longgang), No. 1 Dayun Road, Longgang District, Shenzhen 518172, Guangdong Province, China.
Received: June 8, 2026
Revised: June 27, 2026
Accepted: August 20, 2026
Published online: November 15, 2026
Processing time: 144 Days and 0.6 Hours
Revised: June 27, 2026
Accepted: August 20, 2026
Published online: November 15, 2026
Processing time: 144 Days and 0.6 Hours
Core Tip
Core Tip: This study integrated ferroptosis- and mitochondria-related genes to characterize hepatocellular carcinoma heterogeneity and develop a six-gene prognostic score. Four molecular subtypes showed distinct survival and immune score patterns. Internal validation supported short- and intermediate-term discrimination, whereas performance weakened at 5 years, and Kaplan-Meier separation after risk-group dichotomization was not statistically significant in the external cohorts. The principal contribution is a compact, biologically interpretable framework linking ferroptosis, mitochondrial dysfunction, immune remodeling, and metabolic pathway alterations in hepatocellular carcinoma.