Metabolomic landscape of renal cell carcinoma in von Hippel-Lindau syndrome in a Chinese cohort
Zedan Zhang,
Yi Wang,
Wuping Yang,
Tao Liu,
Chuandong Wang,
Cong Huang,
Yawei Xu,
Xiaolin Chen,
Jingcheng Zhou,
Yizhou Wang,
Xiaohua Zhou,
Yanqing Gong,
Kan Gong
Affiliations
Zedan Zhang
Department of Urology, Peking University First Hospital, Beijing, China; Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
Yi Wang
Beijing International Center for Mathematical Research and Department of Biostatistics, Peking University, Beijing, China
Wuping Yang
Department of Urology, Peking University First Hospital, Beijing, China; Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
Tao Liu
Department of Urology, Peking University First Hospital, Beijing, China; Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
Chuandong Wang
Department of Urology, Peking University First Hospital, Beijing, China; Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
Cong Huang
Department of Urology, Peking University First Hospital, Beijing, China
Yawei Xu
Department of Urology, Peking University First Hospital, Beijing, China; Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
Xiaolin Chen
Department of Urology, Peking University First Hospital, Beijing, China; Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
Jingcheng Zhou
Department of Urology, Peking University First Hospital, Beijing, China; Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
Yizhou Wang
Department of Urology, Peking University First Hospital, Beijing, China; Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
Xiaohua Zhou
Beijing International Center for Mathematical Research and Department of Biostatistics, Peking University, Beijing, China; Corresponding author
Yanqing Gong
Department of Urology, Peking University First Hospital, Beijing, China; Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China; Corresponding author
Kan Gong
Department of Urology, Peking University First Hospital, Beijing, China; Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China; Corresponding author
Summary: Von Hippel-Lindau (VHL) syndrome is a rare autosomal dominant disorder, where renal cell carcinoma (RCC) serves as a significant cause of mortality. We collected peripheral blood from 61 VHL-RCC patients and 31 healthy individuals, along with 19 paired RCC tumor and adjacent non-malignant samples. Using liquid chromatography-mass spectrometry, we identified 238 plasma and 241 tissue differentially abundant metabolites (DAMs), highlighting key pathways such as arginine and proline metabolism. The top 10 of the 23 DAMs, common to both plasma and tissue, were instrumental in constructing a high-performance diagnostic model. These DAMs demonstrated significant correlations with VHL gene mutation types. Cox regression analysis revealed that plasma levels of N2,N2-dimethylguanosine were associated with the timing of RCC onset in VHL patients, acting as an independent predictive factor. This study enhances diagnostic accuracy for this rare condition and opens new avenues for exploring metabolic mechanisms of the disease and potential therapeutic directions.
