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.
Comprehensive molecular profiling of FH-deficient renal cell carcinoma identifies molecular subtypes and potential therapeutic targets.
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作者：Zhang Xingming, Zhao Junjie, Yin Xiaoxue, Liang Jiayu, Wang Yongquan, Zheng Linmao, Tan Ping, Lin Yifei, Xu Nanwei, Zhu Sha, Chen Junru, Zhao Jinge, Hu Xu, Pan Xiuyi, Nie Ling, Zhang Mengni, Chen Yuntian, Zhang Yaowen, Liu Haoyang, Dai Jindong, Wang Zhipeng, Liu Haolin, Ni Yuchao, Rupp Niels J, Moch Holger, Sheng Xinan, Gong Kan, Liu Xiaodong, Chen Zhibin, He Zhengyu, Wang Yaodong, Xu Lijing, Liu Mingsheng, Zhou Hongqing, Tang Bo, Huang Rui, Wei Qiang, Li Xiang, Liu Jiyan, Yao Jin, Liao Banghua, Liu Zhenhua, Shen Pengfei, Chen Ni, Zeng Hao, Sun Guangxi
| 期刊： | Nature Communications | 影响因子： | 15.700 |
| 时间： | 2025 | 起止号： | 2025 May 12; 16(1):4398 |
| doi： | 10.1038/s41467-025-59513-8 | ||
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