Molecular characterization of renal cell carcinoma: A potential three-MicroRNA prognostic signature

Soum D. Lokeshwar, Asif Talukder, Travis J. Yates, Martin J.P. Hennig, Michael Garcia-Roig, Sarrah S. Lahorewala, Naureen N. Mullani, Zachary W A Klaassen, Bruce R. Kava, Murugesan Manoharan, Mark S. Soloway, Vinata B Lokeshwar

Research output: Contribution to journalEditorial

10 Citations (Scopus)

Abstract

Background: Aberrantly expressed miRNAs 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 an miRNA signature for predicting clinical outcome in RCC patients, we used a four-pronged interconnected approach. Methods: Differentially expressed miRNAs 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 miRNAs were analyzed by qPCR, and their levels were correlated with RCC subtypes and clinical outcome. miRNA signature was confirmed in The Cancer Genome Atlas RCC dataset (n ¼ 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 and miR-194 as downregulated (3–60-fold) in RCC; miR-155 distinguished small tumors (<4 cm) from benign oncocytomas. In univariate and multivariate analyses, miRNA combinations (miR-21þ194; miR-21þ142-5pþ194) significantly predicted metastasis and/or disease-specific mortality; miR-21þ142-5pþ194 (for metastasis): P ¼ 0.0017; OR, 0.53; 95% confidence interval (CI), 0.75–0.33; 86.7% sensitivity; 82% specificity. In the TCGA dataset, combined biomarkers associated with metastasis and overall survival (miR-21þ142-5pþ194: P < 0.0001; OR, 0.37; 95% CI, 0.58–0.23). Conclusions: The interconnected discovery–validation approach identified a three-miRNA 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 three-miRNA signature discovered and validated may potentially at an early stage detect and predict metastasis, to allow early intervention for improving patient prognosis.

Original languageEnglish (US)
Pages (from-to)464-472
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume27
Issue number4
DOIs
StatePublished - Apr 1 2018

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MicroRNAs
Renal Cell Carcinoma
Neoplasm Metastasis
Neoplasms
Biomarkers
Confidence Intervals
Oxyphilic Adenoma
Survival
Atlases
Down-Regulation
Multivariate Analysis
Genome
Kidney
Mortality
Growth

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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Molecular characterization of renal cell carcinoma : A potential three-MicroRNA prognostic signature. / Lokeshwar, Soum D.; Talukder, Asif; Yates, Travis J.; Hennig, Martin J.P.; Garcia-Roig, Michael; Lahorewala, Sarrah S.; Mullani, Naureen N.; Klaassen, Zachary W A; Kava, Bruce R.; Manoharan, Murugesan; Soloway, Mark S.; Lokeshwar, Vinata B.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 27, No. 4, 01.04.2018, p. 464-472.

Research output: Contribution to journalEditorial

Lokeshwar, SD, Talukder, A, Yates, TJ, Hennig, MJP, Garcia-Roig, M, Lahorewala, SS, Mullani, NN, Klaassen, ZWA, Kava, BR, Manoharan, M, Soloway, MS & Lokeshwar, VB 2018, 'Molecular characterization of renal cell carcinoma: A potential three-MicroRNA prognostic signature', Cancer Epidemiology Biomarkers and Prevention, vol. 27, no. 4, pp. 464-472. https://doi.org/10.1158/1055-9965.EPI-17-0700
Lokeshwar, Soum D. ; Talukder, Asif ; Yates, Travis J. ; Hennig, Martin J.P. ; Garcia-Roig, Michael ; Lahorewala, Sarrah S. ; Mullani, Naureen N. ; Klaassen, Zachary W A ; Kava, Bruce R. ; Manoharan, Murugesan ; Soloway, Mark S. ; Lokeshwar, Vinata B. / Molecular characterization of renal cell carcinoma : A potential three-MicroRNA prognostic signature. In: Cancer Epidemiology Biomarkers and Prevention. 2018 ; Vol. 27, No. 4. pp. 464-472.
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title = "Molecular characterization of renal cell carcinoma: A potential three-MicroRNA prognostic signature",
abstract = "Background: Aberrantly expressed miRNAs 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 an miRNA signature for predicting clinical outcome in RCC patients, we used a four-pronged interconnected approach. Methods: Differentially expressed miRNAs 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 miRNAs were analyzed by qPCR, and their levels were correlated with RCC subtypes and clinical outcome. miRNA signature was confirmed in The Cancer Genome Atlas RCC dataset (n ¼ 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 and miR-194 as downregulated (3–60-fold) in RCC; miR-155 distinguished small tumors (<4 cm) from benign oncocytomas. In univariate and multivariate analyses, miRNA combinations (miR-21{\th}194; miR-21{\th}142-5p{\th}194) significantly predicted metastasis and/or disease-specific mortality; miR-21{\th}142-5p{\th}194 (for metastasis): P ¼ 0.0017; OR, 0.53; 95{\%} confidence interval (CI), 0.75–0.33; 86.7{\%} sensitivity; 82{\%} specificity. In the TCGA dataset, combined biomarkers associated with metastasis and overall survival (miR-21{\th}142-5p{\th}194: P < 0.0001; OR, 0.37; 95{\%} CI, 0.58–0.23). Conclusions: The interconnected discovery–validation approach identified a three-miRNA 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 three-miRNA signature discovered and validated may potentially at an early stage detect and predict metastasis, to allow early intervention for improving patient prognosis.",
author = "Lokeshwar, {Soum D.} and Asif Talukder and Yates, {Travis J.} and Hennig, {Martin J.P.} and Michael Garcia-Roig and Lahorewala, {Sarrah S.} and Mullani, {Naureen N.} and Klaassen, {Zachary W A} and Kava, {Bruce R.} and Murugesan Manoharan and Soloway, {Mark S.} and Lokeshwar, {Vinata B}",
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T1 - Molecular characterization of renal cell carcinoma

T2 - A potential three-MicroRNA prognostic signature

AU - Lokeshwar, Soum D.

AU - Talukder, Asif

AU - Yates, Travis J.

AU - Hennig, Martin J.P.

AU - Garcia-Roig, Michael

AU - Lahorewala, Sarrah S.

AU - Mullani, Naureen N.

AU - Klaassen, Zachary W A

AU - Kava, Bruce R.

AU - Manoharan, Murugesan

AU - Soloway, Mark S.

AU - Lokeshwar, Vinata B

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Background: Aberrantly expressed miRNAs 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 an miRNA signature for predicting clinical outcome in RCC patients, we used a four-pronged interconnected approach. Methods: Differentially expressed miRNAs 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 miRNAs were analyzed by qPCR, and their levels were correlated with RCC subtypes and clinical outcome. miRNA signature was confirmed in The Cancer Genome Atlas RCC dataset (n ¼ 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 and miR-194 as downregulated (3–60-fold) in RCC; miR-155 distinguished small tumors (<4 cm) from benign oncocytomas. In univariate and multivariate analyses, miRNA combinations (miR-21þ194; miR-21þ142-5pþ194) significantly predicted metastasis and/or disease-specific mortality; miR-21þ142-5pþ194 (for metastasis): P ¼ 0.0017; OR, 0.53; 95% confidence interval (CI), 0.75–0.33; 86.7% sensitivity; 82% specificity. In the TCGA dataset, combined biomarkers associated with metastasis and overall survival (miR-21þ142-5pþ194: P < 0.0001; OR, 0.37; 95% CI, 0.58–0.23). Conclusions: The interconnected discovery–validation approach identified a three-miRNA 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 three-miRNA signature discovered and validated may potentially at an early stage detect and predict metastasis, to allow early intervention for improving patient prognosis.

AB - Background: Aberrantly expressed miRNAs 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 an miRNA signature for predicting clinical outcome in RCC patients, we used a four-pronged interconnected approach. Methods: Differentially expressed miRNAs 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 miRNAs were analyzed by qPCR, and their levels were correlated with RCC subtypes and clinical outcome. miRNA signature was confirmed in The Cancer Genome Atlas RCC dataset (n ¼ 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 and miR-194 as downregulated (3–60-fold) in RCC; miR-155 distinguished small tumors (<4 cm) from benign oncocytomas. In univariate and multivariate analyses, miRNA combinations (miR-21þ194; miR-21þ142-5pþ194) significantly predicted metastasis and/or disease-specific mortality; miR-21þ142-5pþ194 (for metastasis): P ¼ 0.0017; OR, 0.53; 95% confidence interval (CI), 0.75–0.33; 86.7% sensitivity; 82% specificity. In the TCGA dataset, combined biomarkers associated with metastasis and overall survival (miR-21þ142-5pþ194: P < 0.0001; OR, 0.37; 95% CI, 0.58–0.23). Conclusions: The interconnected discovery–validation approach identified a three-miRNA 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 three-miRNA signature discovered and validated may potentially at an early stage detect and predict metastasis, to allow early intervention for improving patient prognosis.

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