Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Epidemiol Biomarkers Prev. 2018 Feb 12. pii: cebp.0700.2017. doi: 10.1158/1055-9965.EPI-17-0700. [Epub ahead of print]

Molecular Characterization of Renal Cell Carcinoma: A Potential three microRNA Prognostic Signature.

Author information

1
Honors Program in Medical Education, University of Miami, Miller School of Medicine.
2
Department of Surgery, Medical College of Georgia, Augusta University.
3
Department of Cancer Biology, University of Pennsylvania.
4
Department of Urology, University of Schleswig-Holstein.
5
Georgia Pediatric Urology, Children's Healthcare of Atlanta, Emory University.
6
Division of Urology, Department of Surgery, Medical College of Georgia, Augusta University.
7
Georgia Pediatric Urology, Children's Healthcare of Atlanta, University of Miami, Miller School of Medicine.
8
Division of Urologic Oncology Surgery, Miami Cancer Institute, Baptist Health South Florida.
9
Memorial Healthcare System.
10
Honors Program in Medical Education, University of Miami, Miller School of Medicine vlokeshwar@gru.edu.

Abstract

BACKGROUND:

Aberrantly expressed microRNAs (miR) promote renal cell carcinoma (RCC) growth and metastasis and are potentially useful biomarkers for metastatic disease. However, a consensus clinically significant miRNA signature has not been identified. To identify a miRNA signature for predicting clinical outcome in RCC patients we used a four-pronged interconnected approach.

METHODS:

Differentially expressed miRs were identified and analyzed in 113 specimens (Normal kidney: 59; tumor: 54). miRNA-profiling was performed in matched normal and tumor specimens from 8 patients and extended to 32 specimens. Seven aberrantly expressed miRs were analyzed by qPCR and their levels were correlated with RCC subtypes, and clinical outcome. miRNA signature was confirmed in a TCGA RCC-dataset (n=241).

RESULTS:

Discovery phase identified miR-21, miR-142-3p, miR-142-5p, miR-150 and miR-155 as significantly upregulated (2-4-fold) and miR-192, miR-194 as downregulated (3-60-fold) in RCC; miR-155 distinguished small tumors (< 4 cm) from benign oncocytomas. In univariate and multivariate analyses, miR combinations (miR-21+194; miR-21+142-5p+194) significantly predicted metastasis and/or disease-specific mortality; miR-21+142-5p+194 (for metastasis): P=0.0017; OR: 0.53; 95% CI: 0.75 - 0.33; 86.7% sensitivity; 82% specificity. In the TCGA dataset, combined biomarkers associated with metastasis and overall survival (miR-21+142-5p+194: P<0.0001; OR: 0.37; 95% CI: 0.58 - 0.23).

CONCLUSION:

The interconnected discovery-validation approach identified a 3-miR signature as a potential predictor of disease outcome in RCC patients.

IMPACT:

With 10% survival at 5-years, metastatic disease presents poor prognosis for RCC patients. The 3 miRNA signature discovered and validated may potentially early detect and predict metastasis, to allow early intervention for improving patient prognosis.

PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center