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8. A Novel Cuproptosis-Related Prognostic Model and the Hub Gene FDX1 Predict the Prognosis and Correlate with Immune Infiltration in Clear Cell Renal Cell Carcinoma

Author

Zhang, Kenan, primary, Yang, Wuping, additional, Zhang, Zedan, additional, Ma, Kaifang, additional, Li, Lei, additional, Xu, Yawei, additional, Qiu, Jianhui, additional, Yu, Chaojian, additional, Zhou, Jingcheng, additional, Cai, Lin, additional, Gong, Yanqing, additional, and Gong, Kan, additional

Published
2022
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12. Additional file 1 of VHL Ser65 mutations enhance HIF2α signaling and promote epithelial-mesenchymal transition of renal cancer cells

Author

Ma, Xueyou, Tan, Zenglai, Zhang, Qin, Ma, Kaifang, Xiao, Jun, Wang, Xiong, Wang, Yanan, Zhong, Mengjie, Wang, Yu, Li, Jing, Zeng, Xing, Guan, Wei, Wang, Shaogang, Gong, Kan, Wei, Gong-Hong, and Wang, Zhihua

Subjects
macromolecular substances
Abstract

Additional file 1: Figure S1. (A) Quantitative of HIF-2α expression levels in 786-O cells stably expressing VHL WT and mutants, with or without treatment of MG132. The western blot images were scanning densitometric values were obtained using ImageJ software. HIF-2α Protein levels were normalized to the loading control β-ACTIN. (B) Interaction of HIF-2α with VHL-WT and mutants after MG132 treatment. (C) Western blot for HIF-2α expression in 786-O cells treated with or without hypoxia mimetic CoCl2 and DMOG. CoCl2 was used at 100 uM final concentration for 6 h, DMOG was used at 1 mM final concentration for 8 h. (D) Immunostaining of FLAG-VHL in 786-O cells with and without MG132 treatment, Scale bars, 50 μm.

Published
2022
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13. Additional file 5 of VHL Ser65 mutations enhance HIF2α signaling and promote epithelial-mesenchymal transition of renal cancer cells

Author

Ma, Xueyou, Tan, Zenglai, Zhang, Qin, Ma, Kaifang, Xiao, Jun, Wang, Xiong, Wang, Yanan, Zhong, Mengjie, Wang, Yu, Li, Jing, Zeng, Xing, Guan, Wei, Wang, Shaogang, Gong, Kan, Wei, Gong-Hong, and Wang, Zhihua

Subjects
urologic and male genital diseases, female genital diseases and pregnancy complications
Abstract

Additional file 5: Figure S5. Gene set enrichment analysis (GSEA) analysis identifies significant common (A and B) and distinct Hallmark signatures between VHL-deficiency and VHL-S65P/W (C and D). Gene signatures with FDR

Published
2022
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15. Additional file 2 of VHL Ser65 mutations enhance HIF2α signaling and promote epithelial-mesenchymal transition of renal cancer cells

Author

Ma, Xueyou, Tan, Zenglai, Zhang, Qin, Ma, Kaifang, Xiao, Jun, Wang, Xiong, Wang, Yanan, Zhong, Mengjie, Wang, Yu, Li, Jing, Zeng, Xing, Guan, Wei, Wang, Shaogang, Gong, Kan, Wei, Gong-Hong, and Wang, Zhihua

Abstract

Additional file 2: Figure S2. (A-B) GSEA-determined hypoxia (A) or glycolysis (B) pathways with S65P-affected gene signature. Genes are ranked by their expression levels in 786-O cells expressing VHL mutation S65P. Plots in the right of A or B show HIF2α ChIP-seq signals of 5 kb around the transcriptional start sites (TSS) of altered genes in hypoxia (A) or glycolysis (B) pathways. (C) VIM or CDH1 is upregulated or downregulated in KIRC patient samples, respectively.

Published
2022
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16. Additional file 4 of VHL Ser65 mutations enhance HIF2α signaling and promote epithelial-mesenchymal transition of renal cancer cells

Author

Ma, Xueyou, Tan, Zenglai, Zhang, Qin, Ma, Kaifang, Xiao, Jun, Wang, Xiong, Wang, Yanan, Zhong, Mengjie, Wang, Yu, Li, Jing, Zeng, Xing, Guan, Wei, Wang, Shaogang, Gong, Kan, Wei, Gong-Hong, and Wang, Zhihua

Subjects
urologic and male genital diseases
Abstract

Additional file 4: Figure S4. (A-C) The sum expression levels of VHL-S65W signature gene set are significantly upregulated in human renal cancers compared to normal kidney samples. (D,E) The sum expression levels of VHL-S65W genetic signature positively correlate with EMT scores in the two independent clinical cohorts of ccRCC patient group.

Published
2022
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17. Additional file 3 of VHL Ser65 mutations enhance HIF2α signaling and promote epithelial-mesenchymal transition of renal cancer cells

Author

Ma, Xueyou, Tan, Zenglai, Zhang, Qin, Ma, Kaifang, Xiao, Jun, Wang, Xiong, Wang, Yanan, Zhong, Mengjie, Wang, Yu, Li, Jing, Zeng, Xing, Guan, Wei, Wang, Shaogang, Gong, Kan, Wei, Gong-Hong, and Wang, Zhihua

Subjects
urologic and male genital diseases
Abstract

Additional file 3: Figure S3. (A-D) The sum expression levels of VHL-S65P signature gene set are significantly upregulated in human renal cancers compared to normal kidney samples.

Published
2022
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23. Genotype–phenotype correlations and clinical outcomes of patients with von Hippel-Lindau disease with large deletions

Author

Zhang, Kenan, Yang, Wuping, Ma, Kaifang, Qiu, Jianhui, Li, Lei, Xu, Yawei, Zhang, Zedan, Yu, Chaojian, Zhou, Jingcheng, Gong, Yanqing, Cai, Lin, and Gong, Kan

Abstract

BackgroundApproximately 20%–40% of patients with von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary disease, exhibit large deletions (LDs). Few studies have focused on this population. Hence, we aimed to elucidate the genotype–phenotype correlations and clinical outcomes in VHL patients with LDs.MethodsIn this retrospective study, we included 119 patients with VHL disease from 50 unrelated families in whom LDs were detected using traditional and next-generation sequencing methods. Other germline mutations were confirmed by Sanger sequencing. Genotype–phenotype correlations and survival were analysed in different groups using Kaplan-Meier and Cox regression. We also evaluated therapeutic response to tyrosine kinase inhibitor (TKI) therapy.ResultsThe overall penetrance of patients aged <60 was 95.2%. Two VHL patients with LDs also carried CHEK2and FLCNgermline mutations. An earlier age of onset of retinal haemangioblastoma was observed in the next generation. Patients with exon 2 deletion of VHLhad an earlier onset age of renal cell carcinoma and pancreatic lesions. The risk of renal cell carcinoma was lower in VHL patients with LDs and a BRK1deletion. The group with earlier age of onset received poorer prognosis. Four of eight (50%) patients showed partial response to TKI therapy.ConclusionThe number of generations and the status of exon 2 could affect age of onset of VHL-related manifestations. Onset age was an independent risk factor for overall survival. TKI therapy was effective in VHL patients with LDs. Our findings would further support clinical surveillance and decision-making processes.

Published
2023
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37. The Efficacy and Safety of Tyrosine Kinase Inhibitors for Von Hippel–Lindau Disease: A Retrospective Study of 32 Patients

Author

Ma, Kaifang, primary, Hong, Baoan, additional, Zhou, Jingcheng, additional, Gong, Yanqing, additional, Wang, Jiangyi, additional, Liu, Shengjie, additional, Peng, Xiang, additional, Zhou, Bowen, additional, Zhang, Jiufeng, additional, Xie, Haibiao, additional, Zhang, Kenan, additional, Li, Lei, additional, Cai, Desheng, additional, Wang, Zixin, additional, Cai, Lin, additional, and Gong, Kan, additional

Published
2019
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40. Intra-Familial Phenotypic Heterogeneity and Telomere Abnormality in von Hippel- Lindau Disease: Implications for Personalized Surveillance Plan and Pathogenesis of VHL-Associated Tumors

Author

Wang, Jiangyi, primary, Peng, Xiang, additional, Chen, Cen, additional, Ning, Xianghui, additional, Peng, Shuanghe, additional, Li, Teng, additional, Liu, Shengjie, additional, Hong, Baoan, additional, Zhou, Jingcheng, additional, Ma, Kaifang, additional, Cai, Lin, additional, and Gong, Kan, additional

Published
2019
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49. Clinical characteristics and risk factors for survival in affected offspring of von Hippel-Lindau disease patients

Author

Zhang, Kenan, Qiu, Jianhui, Yang, Wuping, Ma, Kaifang, Li, Lei, Xie, Haibiao, Xu, Yawei, Gong, Yanqing, Zhou, Jingcheng, Cai, Lin, and Gong, Kan

Abstract

BackgroundVon Hippel-Lindau (VHL) disease is an autosomal dominant genetic tumour syndrome with poor prognosis. The clinical manifestation was found to be more serious in affected offspring of patients with VHL disease, but the risk factors and survival for them have never been reported before. We aimed to explore how these patients were influenced by genetic and clinical factors.MethodsIn this retrospective study, we collected 372 affected offspring of VHL patients from 118 unrelated VHL families. Patients were stratified into different groups based on sets of variables. The age-related risk, overall survival and central nervous systemhaemangioblastoma (CHB)-specific survival were analysed between different groups using Kaplan-Meier survival analysis and Cox regression analysis.ResultsThe estimated median life expectancy and median age of onset for affected offspring of VHL patients were 66 years and 28 years, respectively. The later generation and patients with mutations in exon 3 had an earlier onset age. The first presenting symptom was the only independent risk factor influencing overall survival and CHB-specific survival. Patients that the first presenting symptom is central nervous system (CNS) significantly had a lower life expectancy both in overall survival and CHB-specific survival analysis than abdominal lesions group.ConclusionThis study indicated that affected offspring of VHL patients with CNS as the first presenting symptom was an independent risk factor for overall survival and CHB-specific survival. Generation and mutation region only had an effect on the onset age, which is helpful to clinical decision-making and generate a more precise surveillance protocol.

Published
2022
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50. Distinctive clinicopathological features of Von Hippel-Lindau-associated hereditary renal cell carcinoma: A single-institution study.

Author

Hong, Baoan, Zhang, Zhongyuan, Zhou, Jingcheng, Ma, Kaifang, Zhang, Jiufeng, Cai, Lin, Zhang, Ning, and Gong, Kan

Subjects
VON Hippel-Lindau disease, RENAL cell carcinoma, CYSTIC kidney disease, TUMOR grading, GENETIC disorders
Abstract

Von Hippel-Lindau (VHL) disease is a genetic syndrome that involves the development of tumors in numerous organs. The kidney is one of the most frequently affected organs, and patients with VHL and renal tumors require repeated nephrectomy. The present study aimed to further determine the clinicopathological characteristics of patients with VHL-associated renal cell carcinoma (RCC), which may allow more rational clinical treatment decisions. This study included 27 patients with VHL who underwent radical or partial nephrectomy at the Peking University First Hospital between January 2010 and April 2018. The clinicopathological characteristics and prognosis of the patients were retrospectively reviewed. The expression of RCC-associated molecular markers was evaluated by immunohistochemistry. The mean size of the renal tumors was 4.3±2.0 cm (range 1.3–9.5 cm). The pathological type in 26 cases (96.3%) was clear cell RCC (CCRCC), whereas only one patient was diagnosed with CCRCC and clear cell papillary RCC. Renal cysts with a clear cell lining were observed, and RCC cell clusters were scattered in renal cyst cavities. Among the 27 patients, 21 (77.8%) were diagnosed with stage IA/T1N0M0, according to Tumor-Node-Metastasis staging, and 16 (59.3%) had grade 1 tumors. The mean postoperative follow-up duration was 39.0±24.0 months (range, 1.7–96.5 months). No metastasis or VHL-associated mortality was observed. VHL-associated RCC is a relatively low-risk disease, and a tumor size of 4 cm was determined as a threshold for nephron-sparing surgery. In addition, to prevent tumor cell dispersion, renal cysts should be carefully treated. A comprehensive understanding of the clinicopathological characteristics and underlying mechanisms of RCC associated with VHL syndrome may improve patient prognosis. [ABSTRACT FROM AUTHOR]

Published
2019

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