Scholarlink

<p>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 <i>FH</i> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Comprehensive molecular profiling of FH-deficient renal cell carcinoma identifies molecular subtypes and potential therapeutic targets

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月12日

查看全文
  • Xingming Zhang,
  • Junjie Zhao,
  • Xiaoxue Yin,
  • Jiayu Liang,
  • Yongquan Wang,
  • Linmao Zheng,
  • Ping Tan,
  • Yifei Lin,
  • Nanwei Xu,
  • Sha Zhu,
  • Junru Chen,
  • Jinge Zhao,
  • Xu Hu,
  • Xiuyi Pan,
  • Ling Nie,
  • Mengni Zhang,
  • Yuntian Chen,
  • Yaowen Zhang,
  • Haoyang Liu,
  • Jindong Dai,
  • Zhipeng Wang,
  • Haolin Liu,
  • Yuchao Ni,
  • Niels J. Rupp,
  • Holger Moch,
  • Xinan Sheng,
  • Kan Gong,
  • Xiaodong Liu,
  • Zhibin Chen,
  • Zhengyu He,
  • Yaodong Wang,
  • Lijing Xu,
  • Mingsheng Liu,
  • Hongqing Zhou,
  • Bo Tang,
  • Rui Huang,
  • Qiang Wei,
  • Xiang Li,
  • Jiyan Liu,
  • Jin Yao,
  • Banghua Liao,
  • Zhenhua Liu,
  • Pengfei Shen,
  • Ni Chen,
  • Hao Zeng,
  • Guangxi Sun

摘要

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.