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Plasma exosomal miRNAs-based prognosis in metastatic kidney cancer. Oncotarget 2017 Sep 08;8(38):63703-63714

Date

10/04/2017

Pubmed ID

28969022

Pubmed Central ID

PMC5609954

DOI

10.18632/oncotarget.19476

Scopus ID

2-s2.0-85028376284   33 Citations

Abstract

Plasma exosomal miRNAs were evaluated for prognosis in an initial set of 44 metastatic renal cell cancer (mRCC) patients by RNA sequencing. Among a??3.49 million mappable reads per patient, miRNAs accounted for 93.1% of the mapped RNAs. 227 miRNAs with high abundance were selected for survival analysis. Cox regression analysis identified association of 6 miRNAs with overall survival (OS) (P<0.01, False discovery rate (FDR) < 0.3). Five of the associated miRNAs were quantified in an independent follow-up cohort of 65 mRCC patients by TaqMan-based miRNA assays. Kaplan-Meier analysis confirmed the significant OS association of three miRs; miR-let-7i-5p (P=0.018, HR=0.49, 95% CI=0.21-0.84), miR-26a-1-3p (P=0.025, HR=0.43, 95% CI=0.10-0.84) and miR-615-3p (P=0.0007, HR=0.36, 95% CI=0.11-0.54). A multivariate analysis of miR-let-7i-5p with the clinical factor-based Memorial Sloan-Kettering Cancer Center (MSKCC) score improved survival prediction from an area under the curve (AUC) of 0.58 for MSKCC score to an average AUC of 0.64 across 48-month follow-up time. The multivariate model was able to define a high-risk group with median survival of 14 months and low risk group of 39 months (P=0.0002, HR=3.43, 95%CI, 2.73-24.15). Further validation of miRNA-based prognostic biomarkers are needed to improve current clinic-pathologic based prognostic models in patients with mRCC.

Author List

Du M, Giridhar KV, Tian Y, Tschannen MR, Zhu J, Huang CC, Kilari D, Kohli M, Wang L

Author

Deepak Kilari MD Associate Professor in the Medicine department at Medical College of Wisconsin