Research Papers:

Plasma exosomal miRNAs-based prognosis in metastatic kidney cancer

Meijun Du, Karthik V. Giridhar, Yijun Tian, Michael R. Tschannen, Jing Zhu, Chiang-Ching Huang, Deepak Kilari, Manish Kohli and Liang Wang _

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Oncotarget. 2017; 8:63703-63714. https://doi.org/10.18632/oncotarget.19476

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Meijun Du1,*, Karthik V. Giridhar2,*, Yijun Tian1,3, Michael R. Tschannen4, Jing Zhu1, Chiang-Ching Huang5, Deepak Kilari6, Manish Kohli2 and Liang Wang1

1Department of Pathology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA

2Department of Oncology, Mayo Clinic, Rochester, MN, USA

3Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China

4Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA

5Department of Biostatistics, University of Wisconsin, Milwaukee, WI, USA

6Department of Oncology, Medical College of Wisconsin and Milwaukee VA Medical Center, Milwaukee, WI, USA

*These authors have contributed equally to this work

Correspondence to:

Liang Wang, email: [email protected]

Manish Kohli, email: [email protected]

Keywords: metastatic renal cell cancer, exosomal miRNA, overall survival, biomarker

Received: March 28, 2017    Accepted: June 19, 2017    Published: July 22, 2017


Plasma exosomal miRNAs were evaluated for prognosis in an initial set of 44 metastatic renal cell cancer (mRCC) patients by RNA sequencing. Among ~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.

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