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Int. J. Mol. Sci. 2017, 18(11), 2326; https://doi.org/10.3390/ijms18112326

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma

1
Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
2
Biomarker Discovery, Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA
3
Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
4
Department of Oncology, Clínica Santa María, Santiago 8320000, Chile
5
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 5 October 2017 / Revised: 28 October 2017 / Accepted: 31 October 2017 / Published: 3 November 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset. Cox regression multivariate analysis confirmed that two of the candidate genes were significantly associated with overall survival. Higher expression of BAG1 [hazard ratio (HR) of 0.14, p < 0.0001, 95% confidence interval (CI) 0.04–0.36] and NOP56 (HR 0.13, p < 0.0001, 95% CI 0.05–0.34) were associated with better prognosis. A prognostic model incorporating expression of BAG1 and NOP56 into the MSKCC score improved prognostication significantly over a model using the MSKCC prognostic score only (p < 0.0001). Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies. View Full-Text
Keywords: metastatic renal cell carcinoma; prognostic biomarkers; whole blood mRNA gene expression metastatic renal cell carcinoma; prognostic biomarkers; whole blood mRNA gene expression
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Giridhar, K.V.; Sosa, C.P.; Hillman, D.W.; Sanhueza, C.; Dalpiaz, C.L.; Costello, B.A.; Quevedo, F.J.; Pitot, H.C.; Dronca, R.S.; Ertz, D.; Cheville, J.C.; Donkena, K.V.; Kohli, M. Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma. Int. J. Mol. Sci. 2017, 18, 2326.

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