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

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Teixeira, AL (Author) Other; Ferreira, M (Author) Other; Silva, J (Author) Other; Gomes, M (Author) Other; Dias, F (Author) Other; Santos, JI (Author) Other; Mauricio, J (Author) Other; Lobo, F (Author) Other; Rui Medeiros (Author) ICBAS

Journal

Title: Tumor Biology

Vol. 35

Pages: 4057-4066

ISSN: 1010-4283

Publisher: SAGE

Indexing

ISI Web of Knowledge - 87 Citations

Scopus - 92 Citations

Other information

Authenticus ID: P-009-GH3

DOI: 10.1007/s13277-013-1531-3

Abstract (EN): 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(-Delta Delta Ct) = 2.8, P = 0.028; 2(-Delta Delta Ct) = 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(-Delta Delta Ct) = 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 (a parts per thousand yen60 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10