Low expression of miR-126 is a prognostic marker for metastatic clear cell renal cell carcinoma.

Autor:	Khella HW; Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada., Scorilas A; Department of Biochemistry and Molecular Biology, University of Athens, Athens, Greece., Mozes R; Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada., Mirham L; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada., Lianidou E; Department of Chemistry, University of Athens, Athens, Greece., Krylov SN; Department of Chemistry and Centre for Research on Biomolecular Interactions, York University, Toronto, Ontario, Canada., Lee JY; Division of Urology, St. Michael's Hospital, Toronto, Ontario, Canada., Ordon M; Division of Urology, St. Michael's Hospital, Toronto, Ontario, Canada., Stewart R; Division of Urology, St. Michael's Hospital, Toronto, Ontario, Canada., Jewett MA; Division of Urologic Oncology, Department of Surgery, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada., Yousef GM; Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Electronic address: yousefg@smh.ca.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2015 Mar; Vol. 185 (3), pp. 693-703. Date of Electronic Publication: 2015 Jan 05.
DOI:	10.1016/j.ajpath.2014.11.017
Abstrakt:	Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with unpredictable behavior. Clinical parameters are not always accurate for predicting prognosis. miR-126 is differentially expressed in many cancers, including RCC, and is down-regulated in metastatic versus primary ccRCC. We assessed the prognostic significance of miR-126 in 264 primary ccRCCs. We also compared its expression in normal kidney, primary and metastatic ccRCC, and RCC subtypes. We validated our results on an independent set of 481 ccRCCs. miR-126 was down-regulated in metastatic versus primary tumors and in tumors of higher stage (P = 0.005) or higher grade (P = 0.002). miR-126 up-regulation was associated with significantly prolonged disease-free survival (P < 0.001) and overall survival (P = 0.015). For larger tumors (>4 cm), patients with higher miR-126 expression had significantly longer survival. Restoration of miR-126 expression decreased cellular migration and proliferation in RCC cell lines. The ccRCCs exhibited the highest miR-126 expression, and papillary RCCs exhibited the lowest expression. We identified a number of miR-126 targets and pathways that are involved in carcinogenesis, including the apoptosis signaling pathway. miR-126 is a promising prognostic marker in ccRCC that can distinguish between clear cell and papillary subtypes. In addition, miR-126 has potential therapeutic applications. (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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