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

作　　者：Mengjiao Xu Wen Deng Tingting Jiang Shiyu Wang Ruyu Liu Min Chang Shuling Wu Ge Shen Xiaoxue Chen Yuanjiao Gao Hongxiao Hao Leiping Hu Lu Zhang Yao Lu Wei Yi Yao Xie Minghui Li 

机构地区：[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 3,Peking University Ditan Teaching Hospital,Beijing 100015,China

出　　处：《Biomedical and Environmental Sciences》2025年第3期313-327,共15页生物医学与环境科学(英文版)

基　　金：supported by Beijing Science and Technology Commission(grant number Z211100002921059);National Science and Technology Major Projects of China(2017ZX10201201-001-006,2017ZX10201201-002-006,and 2018ZX10715-005-003-005);Digestive Medical Coordinated Development Center of Beijing Hospital Authority(XXZ0302 and XXT28);National Key R&D Program China(2022YFC2603505);Beijing Hospital Authority Clinical Medicine Development with Special Funding Support(XMLX 202127);High-Level Public Health Technical Personnel Training Program of Beijing the Municipal Health Commission(2022-3-050);Capital Health Research and Development of Special(2022-1-2172).

摘　　要：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.

关 键 词：Hepatocellular carcinoma Ferroptosis Prognostic biomarker IMMUNOTHERAPY 

分 类 号：R73[医药卫生—肿瘤]