Clinicopathologic Significance of VHL Gene Alteration in Clear-Cell Renal Cell Carcinoma: An Updated Meta-Analysis and Review

Abstract

The von Hippel-Lindau (VHL) gene is inactivated frequently in sporadic clear-cell renal cell carcinomas (ccRCCs) by genetic alteration (mutation, loss of heterozygosity, or promoter hypermethylation). However, the pathological or prognostic significance of VHL gene alteration has not been well defined. We conducted this meta-analysis to evaluate the association between VHL alteration and clinopathologic findings in ccRCCs. We performed a systematic computerized search of online databases, including PubMed, EMBASE, Web of Science, and Google Scholar (up to July 2018). From ten studies, 1,082 patients were included in the pooled analyses of odds ratios (ORs) with 95% confidence intervals (CIs) for pathological features (nuclear grade and disease stage) or hazard ratios (HRs) with 95% CIs for overall survival (OS). VHL alteration was not significantly associated with nuclear grade (OR = 0.79, 95% CI: 0.59–1.06, p = 0.12) or disease stage (OR = 1.07, 95% CI: 0.79–1.46, p = 0.65). There was also no significant correlation between VHL alteration and OS (HR = 0.75, 95% CI: 0.43–1.29, p = 0.30). When we pooled HRs for OS according to the VHL alteration types, the combined HRs were 0.72 (95% CI: 0.47–1.11, p = 0.14) for VHL mutations and 1.32 (95% CI: 0.70–2.47, p = 0.39) for methylation. In conclusion, this meta-analysis indicates that VHL gene alteration is not significantly associated with the pathological features and survival in patients with ccRCC.

Integrative radiogenomics analysis for predicting molecular features and survival in clear cell renal cell carcinoma

“…The integration of radiomics and genomics data could be valuable and enable more precise survival prediction. However, the prognostic role of radiomics and other omics features is still controversial, for example, few studies demonstrated that VHL mutation could predict patient survival [ 9 ], and many genes and pathways still lack related evidence. Moreover, the correlation between radiomics and other omics features is complex.…”

“…Several targeted blockers of vascular endothelial growth factor pathway (e.g., sorafenib, axitinib) have been approved for treatment of metastatic RCC [ 8 ]. However, the capability of VHL mutation as a prognostic factor was not significant in ccRCC [ 9 ]. Conversely, PBRM1 mutation was associated with shorter survival, early tumor progression, and response to immune checkpoint therapies in ccRCC patients [ 10 , 11 ].…”

Spectrum of VHL mutations in clear cell renal cell carcinoma

“…Изучение связи мутаций VHL с этиологией, прогрессированием и прогнозом скПКР привело к накоплению большого количества противоречивых данных. Метаанализ результатов 10 публикаций, включивших 1082 пациента со скПКР, показал, что изменения гена VHL незначительно ассоциированы с клиническими характеристиками заболевания и общей выживаемостью пациентов [22]. Тем не менее изучение мутаций VHL важно, так как для прогрессирования скПКР и, возможно, для прогноза заболевания определенное значение имеет сочетание мутаций VHL и других генов [23][24][25].…”

Integrated bioinformatics analysis for the identification of potential key genes affecting the pathogenesis of clear cell renal cell carcinoma

“…In addition, CCRCC has the worst prognosis among the common epithelial kidney tumors ( 5 ). Recently, significant progress has been made in the current understanding of CCRCC development; for example, the von Hippel-Lindau tumor suppressor gene is inactivated frequently by genetic alteration ( 6 ). However, the molecular mechanisms underlying CCRCC pathogenesis remain unknown.…”