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, Liang Wang

Research output: Contribution to journalArticle

14 Scopus 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 ~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; miRlet- 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.

Original languageEnglish (US)
Pages (from-to)63703-63714
Number of pages12
JournalOncotarget
Volume8
Issue number38
DOIs
StatePublished - Jan 1 2017

Keywords

  • Biomarker
  • Exosomal miRNA
  • Metastatic renal cell cancer
  • Overall survival

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Du, M., Giridhar, K. V., Tian, Y., Tschannen, M. R., Zhu, J., Huang, C. C., Kilari, D., Kohli, M., & Wang, L. (2017). Plasma exosomal miRNAs-based prognosis in metastatic kidney cancer. Oncotarget, 8(38), 63703-63714. https://doi.org/10.18632/oncotarget.19476