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Annelies Verbiest Inne Renders Stefano Caruso Gabrielle Couchy Sylvie Job Annouschka Laenen Virginie Verkarre Nathalie Rioux-Leclercq Patrick Schöffski Yann Vano Reza-Thierry Elaidi Evelyne Lerut Maarten Albersen Stéphane Oudard Wolf-Hervé Fridman Catherine Sautès-Fridman Laurence Albigès Agnieszka Wozniak Benoit Beuselinck 《Clinical genitourinary cancer》2019,17(5):e981-e994
IntroductionRecent trials have suggested predictive biomarkers in advanced clear-cell renal cell carcinoma (accRCC): International Metastatic RCC Database Consortium (IMDC) good risk or angiogenic gene signature for sunitinib and IMDC intermediate/poor risk for ipilimumab-nivolumab and T-effector cell signature or sarcomatoid dedifferentiation for atezolizumab-bevacizumab. We hypothesized that earlier described molecular subtypes, ccrcc1 to ccrcc4, could provide similar information as a single generic biomarker and molecularly characterize the heterogeneous intermediate-risk group.Patients and MethodsPatients with accRCC treated with systemic therapies were included. We assessed associations between the 5 biomarkers and their impact on progression-free survival (PFS) and response rate (RR) on first-line sunitinib or pazopanib. The cutoff percentage of sarcomatoid dedifferentiation with optimal discriminative value was determined.ResultsIn total, 430 patients were included (163 with molecular data). The molecular ccrcc2 subtype identified tumors with higher angiogenic gene expression across IMDC risk groups: prevalence was high in IMDC good risk and low in IMDC poor risk (P < .001). Molecular subtype, IMDC, and angiogenic gene expression had comparable C-indices to predict PFS and RR (range, 60%-66%). The ccrcc2 subtype and angiogenic gene expression were positive predictors of PFS in IMDC intermediate-risk patients (P = .006; P = .04). Immune signature did not differ between IMDC groups, but was strongly correlated with molecular subtype (P = .8 and P = .0007). A cutoff value of 25% sarcomatoid differentiation discriminated tumors with distinct molecular characteristics and therapeutic sensitivity.ConclusionIn accRCC, molecular subtypes can explain differences in IMDC risk group, expression of angiogenesis and immune response genes, and sarcomatoid dedifferentiation. They can identify molecularly different patient populations within the heterogeneous IMDC intermediate group and select patients for systemic therapies. 相似文献
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Joubert Bastien Belbezier Aude Haesebaert Julie Rheims Sylvain Ducray François Picard Géraldine Rogemond Véronique Psimaras Dimitri Berzero Giulia Desestret Virginie Honnorat Jérôme 《Journal of neurology》2020,267(7):2083-2089
Journal of Neurology - To assess the long-term outcomes of patients with temporal lobe epilepsy and CSF anti-glutamate decarboxylase antibodies (GAD65-Abs). We retrospectively analyzed the clinical... 相似文献
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