000061716 001__ 61716 000061716 005__ 20190709135448.0 000061716 0247_ $$2doi$$a10.18632/oncotarget.16494 000061716 0248_ $$2sideral$$a99220 000061716 037__ $$aART-2017-99220 000061716 041__ $$aeng 000061716 100__ $$aPuente, J. 000061716 245__ $$aNovel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma 000061716 260__ $$c2017 000061716 5060_ $$aAccess copy available to the general public$$fUnrestricted 000061716 5203_ $$aBackground: Several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. Patients and methods: Multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)=22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset). Objectives were to compare baseline clinical factors in both populations and to correlate tumor expression of selected signaling pathways components with sunitinib PFS. Results: 123 patients were analyzed (97 LR, 26 PR). In the LR cohort, overall response rate was 79% and median duration of best response was 30 months. Median PFS and overall survival were 43.2 (95% confidence intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At baseline PR patients had a significantly lower proportion of nephrectomies, higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time to and higher presence of metastases, and increased Fuhrman grade. Higher levels of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged survival. No statistical significant associations between hsa-miR-23b or hsa-miR-27b and the expression of c-Met were found. Conclusions: Certain mRCC patients treated with sunitinib achieve extremely long-term responses. Favorable baseline hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa-miR-27b, hsa-miR-23b and hsa-miR- 628-5p could be potentially used as biomarkers of sunitinib response. 000061716 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/CB16-12-00228$$9info:eu-repo/grantAgreement/ES/ISCIII/PIE15-00076$$9info:eu-repo/grantAgreement/ES/ISCIII/RETIC-RD12-0036-0009$$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/SAF2015-66015-R 000061716 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000061716 592__ $$a1.942$$b2017 000061716 593__ $$aOncology$$c2017$$dQ1 000061716 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000061716 700__ $$aLaínez, N. 000061716 700__ $$aDueñas, M. 000061716 700__ $$aMéndez-Vidal, M.J. 000061716 700__ $$aEsteban, E. 000061716 700__ $$aCastellano, D. 000061716 700__ $$aMartinez-Fernández, M. 000061716 700__ $$aBasterretxea, L. 000061716 700__ $$aJuan-Fita, M.J. 000061716 700__ $$aAntón, L. 000061716 700__ $$aLeón, L. 000061716 700__ $$0(orcid)0000-0003-0063-1067$$aLambea, J.$$uUniversidad de Zaragoza 000061716 700__ $$aPérez-Valderrama, B. 000061716 700__ $$aVázquez, S. 000061716 700__ $$aSuarez, C. 000061716 700__ $$adel Muro, X.G. 000061716 700__ $$aGallardo, E. 000061716 700__ $$aMaroto, J.P. 000061716 700__ $$aLuz, Samaniego, M. 000061716 700__ $$aSuárez-Paniagua, B. 000061716 700__ $$aSanz, J. 000061716 700__ $$aParamio, J.M. 000061716 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina 000061716 773__ $$g8, 18 (2017), 30410-30421$$pONCOTARGET$$tOncotarget$$x1949-2553 000061716 8564_ $$s5606052$$uhttps://zaguan.unizar.es/record/61716/files/texto_completo.pdf$$yVersión publicada 000061716 8564_ $$s123019$$uhttps://zaguan.unizar.es/record/61716/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000061716 909CO $$ooai:zaguan.unizar.es:61716$$particulos$$pdriver 000061716 951__ $$a2019-07-09-11:39:25 000061716 980__ $$aARTICLE