ArticleNature communications2025
Comprehensive molecular profiling of FH-deficient renal cell carcinoma identifies molecular subtypes and potential therapeutic targets.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed.
- Repurposing Seleno-L-Methionine as a Pleiotropic Immunomodulatory Agent to Overcome TGF-β1/HIF-Driven Immune Evasion in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Translational Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Rare solid tumours as indicators of hereditary cancer syndromes.European journal of human genetics : EJHG · 2026Review
- HIRA loss is frequent but not universal in human fumarate hydratase-deficient renal cell carcinoma and defines divergent oncogenic programs.Biomarker research · 2026Article
- Sterol regulatory element‑binding proteins: Master regulators of lipid metabolic reprogramming in cancer and emerging therapeutic targets (Review).Oncology reports · 2026Review
- Dissecting the molecular landscape of fumarate hydratase-deficient RCC: towards precision oncology.Nature reviews. Urology · 2026Article
- Identification of cancer mini-drivers by deciphering selective landscape in the cancer genome.Briefings in bioinformatics · 2026Article
- Lineage infidelity in FH-deficient RCC with secondary somatic alterations: a case report and implications for diagnosis and treatment.Therapeutic advances in medical oncology · 2026Article
- Fumarate and fumarate hydratase: an immunometabolite regulator of inflammation and diseases.Frontiers in immunology · 2026Review
- Racial differences in kidney cancer histology and outcome: A nationwide study from the UroCCR Cohort.Cancer · 2025Article
- Emerging roles of metabolic biomarkers in renal cell carcinoma: from molecular mechanisms to clinical implications.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
46 authors.
Xingming Zhang *Department of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Junjie Zhao *Department of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Xiaoxue Yin *Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Jiayu Liang *Department of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Yongquan Wang *Department of Urology, Southwest Hospital, Army Medical University, Chongqing, China.
Linmao Zheng *Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Ping TanDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Yifei LinDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Nanwei XuDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Sha ZhuDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Junru ChenDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0003-4553-6979
Jinge ZhaoDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Xu HuDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0003-4306-4656
Xiuyi PanDepartment of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Ling NieDepartment of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Mengni ZhangDepartment of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Yuntian ChenDepartment of Radiology, West China Hospital, Sichuan University, Chengdu, China.
Yaowen ZhangDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Haoyang LiuDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Jindong DaiDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Zhipeng WangDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Haolin LiuDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Yuchao NiDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Niels J RuppDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
Holger MochDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-7986-2839
Xinan ShengKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital and Institute, Beijing, China.ORCID http://orcid.org/0000-0001-9359-0975
Kan GongDepartment of Urology, Peking University First Hospital, Beijing, China.
Xiaodong LiuDepartment of Urology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Zhibin ChenDepartment of Urology, The First People's Hospital of Neijiang, Neijiang, China.
Zhengyu HeDepartment of Urology, Yaan People's Hospital, Yaan, China.
Yaodong WangDepartment of Urology, Mianyang Central Hospital, Mianyang, China.
Lijing XuDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Mingsheng LiuThe Second Ward of Urology, Affiliated Qujing Hospital of Kunming Medical University, Qujing, China.
Hongqing ZhouThe Second Ward of Urology, Affiliated Qujing Hospital of Kunming Medical University, Qujing, China.
Bo TangDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Rui HuangDepartment of Nuclear medicine, West China Hospital, Sichuan University, Chengdu, China.
Qiang WeiDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Xiang LiDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Jiyan LiuDepartment of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0003-4885-5481
Jin YaoDepartment of Urology, Southwest Hospital, Army Medical University, Chongqing, China.ORCID http://orcid.org/0000-0003-3028-9370
Banghua LiaoDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.
Zhenhua LiuDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0003-1926-6020
Pengfei ShenDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China. cdhx510@163.com.ORCID http://orcid.org/0000-0002-0370-0411
Ni ChenDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China. chenni1@163.com.ORCID http://orcid.org/0000-0002-0628-0723
Hao ZengDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China. kucaizeng@163.com.ORCID http://orcid.org/0000-0003-0818-8151
Guangxi SunDepartment of Urology, Institute of Urology, Sichuan Clinical Research Center for kidney and urologic diseases, West China Hospital, Sichuan University, Chengdu, China. sungx077@126.com.ORCID http://orcid.org/0000-0003-3719-2643
Funding
National Natural Science Foundation of China (National Science Foundation of China) NSFC 81872107National Natural Science Foundation of China (National Science Foundation of China) NSFC 82103097National Natural Science Foundation of China (National Science Foundation of China) NSFC 82403766National Natural Science Foundation of China (National Science Foundation of China) NSFC 82472673
Abstract
Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare yet highly lethal kidney cancer. To deepen our understanding of FH-deficient RCC, we conduct a comprehensive integrated genomic study. We analyze the association of FH alteration patterns with tumor heterogeneity and develop a CpG site-specific methylation signature for precise identification of FH-deficient RCC. Transcriptomic analysis unveils three distinctive molecular subtypes characterized by enrichment of immune/Angiogenic/Stromal (C1), WNT/Notch/MAPK (C2), and proliferation/stemness (C3) pathways, respectively. Tumors in C1 derive the most substantial survival benefit from a combination of immune checkpoint blockade (ICB) and anti-angiogenic therapy. Tumors in C2 display moderate response to this therapeutic approach. In contrast, tumors in C3 exhibit an unfavorable response to anti-angiogenic monotherapy and its combination with ICB. These findings contribute to a profound understanding of the aggressive nature of FH-deficient RCC, offering insights into potential precision medicine approaches for disease management.
Indexed as
Carcinoma, Renal CellFumarate HydrataseKidney NeoplasmsAngiogenesis InhibitorsAnimalsCpG IslandsDNA MethylationFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmune Checkpoint InhibitorsMiceTranscriptomeAngiogenesis InhibitorsFumarate HydrataseImmune Checkpoint Inhibitors
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