title: Low expression of miR-126 is a prognostic marker for metastatic clear cell renal cell carcinoma.
abstract: 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.
authors.affiliation: 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.
authors.forename: Heba W Z
authors.initials: HW
authors.lastname: Khella
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, Athens, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.affiliation: 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.
authors.forename: Roy
authors.initials: R
authors.lastname: Mozes
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lorna
authors.initials: L
authors.lastname: Mirham
authors.affiliation: Department of Chemistry, University of Athens, Athens, Greece.
authors.forename: Evi
authors.initials: E
authors.lastname: Lianidou
authors.affiliation: Department of Chemistry and Centre for Research on Biomolecular Interactions, York University, Toronto, Ontario, Canada.
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Krylov
authors.affiliation: Division of Urology, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Jason Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Division of Urology, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Ordon
authors.affiliation: Division of Urology, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Stewart
authors.affiliation: Division of Urologic Oncology, Department of Surgery, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
authors.forename: Michael A S
authors.initials: MA
authors.lastname: Jewett
authors.affiliation: 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.
authors.forename: George M
authors.initials: GM
authors.lastname: Yousef
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D049109:Cell Proliferation; D003937:Diagnosis, Differential; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C527111:MIRN126 microRNA, human; D035683:MicroRNAs