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Higher circulating expression levels of miR-221 associated with poor overall survival in renal cell carcinoma patients

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Tumor Biology

Abstract

The mechanisms involved in renal cell carcinoma (RCC) development and progression remain unclear, and new biomarkers for early detection, follow-up of the disease and prognosis are needed in routine practice to improve the diagnostic and/or prognostic accuracy. There is increasing evidence that microRNAs (miRNAs) are involved in cancer development and progression. The up-regulation of miR-221/222 has been described in several human cancers, and during RCC development, this up-regulation can modulate the metastatic process. Our purpose was to investigate the circulating expression levels of miR-221/222 as potential biomarkers for RCC detection and their influence in patients' overall survival. The circulating miR-221/222 was studied by relative quantification in 77 plasma samples. A follow-up study was undertaken to evaluate the overall survival. We observed that RCC patients presented higher circulating expression levels of miR-221 and miR-222 than healthy individuals (2−ΔΔCt = 2.8, P = 0.028; 2−ΔΔCt = 2.2, P = 0.044, respectively). The RCC patients with metastasis at diagnosis also presented higher circulating expression levels of miR-221 than patients with no metastasis (2−ΔΔCt = 10.9, P = 0.001). We also observed a significantly lower overall survival in patients with higher expression levels of miR-221 (48 vs 116 months, respectively; P = 0.024). Furthermore, multivariate Cox regression analysis using the tumour, nodes and metastasis stage (TNM stage); Fuhrman nuclear grade and age (≥60 years) as covariants demonstrated a higher risk of specific death by cancer in patients who presented higher expression levels of miR-221 (hazard ratio (HR) = 10.7, 95 % confidence interval 1.33–85.65, P = 0.026). The concordance (c) index showed that the definition of profiles that contain information regarding tumour characteristics associated with circulating miR-221 expression information presents an increased capacity to predict the risk of death by RCC (c index model 1, 0.800 vs model 2, 0.961). Our results, which identified the plasma miR-221/222 at variable levels during RCC development, suggest that these miRNAs may have a potential as noninvasive biomarkers of RCC development.

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Acknowledgments

We would like to thank the Liga Portuguesa Contra o Cancro—Centro Regional do Norte (Portuguese League Against Cancer) and FCT—Fundação para a Ciência e Tecnologia. ALT is a doctoral degree grant holder from FCT (SFRH/BD/47381/2008). This project was partially sponsored by an unrestricted educational grant for basic research in Molecular Oncology from AstraZeneca Foundation.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Molecular Oncology Group, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino de Almeida, 4200-072,, Porto, Portugal

    Ana L. Teixeira, Joana Silva, Mónica Gomes, Francisca Dias, Juliana I. Santos & Rui Medeiros

  2. ICBAS, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313,, Porto, Portugal

    Ana L. Teixeira, Mónica Gomes, Francisca Dias, Juliana I. Santos & Rui Medeiros

  3. Medical Oncology Department, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino de Almeida, 4200-072,, Porto, Portugal

    Marta Ferreira & Joaquina Maurício

  4. Research Department, LPCC- Portuguese League Against Cancer (NRNorte), Estrada Interior da Circunvalação 6657, 4200,, Porto, Portugal

    Mónica Gomes & Rui Medeiros

  5. Urology Department, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino de Almeida, 4200-072,, Porto, Portugal

    Francisco Lobo

  6. CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia 296, 4200-150,, Porto, Portugal

    Rui Medeiros

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  1. Ana L. Teixeira
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Correspondence to Rui Medeiros.

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Teixeira, A.L., Ferreira, M., Silva, J. et al. Higher circulating expression levels of miR-221 associated with poor overall survival in renal cell carcinoma patients. Tumor Biol. 35, 4057–4066 (2014). https://doi.org/10.1007/s13277-013-1531-3

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