Comprehensive Analysis of Oncogenic, Prognostic, and Immunological Roles of FANCD2 in Hepatocellular Carcinoma: A Potential Predictor for Survival and Immunotherapy.

Meng Jiao XU; Wen DENG; Ting Ting JIANG; Shi Yu WANG; Ru Yu LIU; Min CHANG; Shu Ling WU; Ge SHEN; Xiao Xue CHEN; Yuan Jiao GAO; Hongxiao HAO; Lei Ping HU; Lu ZHANG; Yao LU; Wei YI; Yao XIE; Ming Hui LI

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Comprehensive Analysis of Oncogenic, Prognostic, and Immunological Roles of FANCD2 in Hepatocellular Carcinoma: A Potential Predictor for Survival and Immunotherapy.

Author: Meng Jiao XU ¹ ; Wen DENG ¹ ; Ting Ting JIANG ¹ ; Shi Yu WANG ¹ ; Ru Yu LIU ¹ ; Min CHANG ¹ ; Shu Ling WU ¹ ; Ge SHEN ¹ ; Xiao Xue CHEN ¹ ; Yuan Jiao GAO ¹ ; Hongxiao HAO ¹ ; Lei Ping HU ¹ ; Lu ZHANG ¹ ; Yao LU ¹ ; Wei YI ² ; Yao XIE ³ ; Ming Hui LI ³
Author Information

1. Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
2. Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
3. Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China;Department of Hepatology Division 3, Peking University Ditan Teaching Hospital, Beijing 100015, China.
Publication Type:Journal Article
Keywords: Ferroptosis; Hepatocellular carcinoma; Immunotherapy; Prognostic biomarker
MeSH: Humans; Carcinoma, Hepatocellular/diagnosis*; Liver Neoplasms/diagnosis*; Immunotherapy; Fanconi Anemia Complementation Group D2 Protein/metabolism*; Prognosis; Male; Female; Middle Aged; Biomarkers, Tumor/metabolism*
From: Biomedical and Environmental Sciences 2025;38(3):313-327
CountryChina
Language:English
Abstract: OBJECTIVE:Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy.
METHODS:Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death.
RESULTS:FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism.
CONCLUSION:To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.