Abstract
Circulating miRNAs are ideal diagnostics and prognostics biomarkers in cancer since altered levels of specific miRNAs have been associated to development/progression of several cancers. Physical activity is a recognized preventive strategy against several cancers, but it may also modify the baseline levels of cancer-associated miRNAs and, hence, may act as a confounding pre-analytical variable. This study aimed at understanding whether physical activity-dependent changes in cancer-associated circulating miRNAs profile could act as a confounding variable. A panel comprising 179 miRNAs was assayed in plasma from 20 highly trained and 10 sedentary men. RT-qPCR data were analyzed with the 2−2ΔΔCT methods and normalized on hsa-miR-320d, as determined by bioinformatics analysis. miRNAs associated with the diagnosis of the most prevalent cancers were considered. Only those miRNAs, relevantly associated with cancers, found ≥2-fold up- or downregulated in highly trained subjects compared to sedentary were disclosed. The results reveal that chronic physical activity determined modifications altering the baseline level of several cancer-associated miRNAs and, hence, their diagnostic and prognostic potential. In conclusion, based on our results, a physically active status emerges as an important pre-analytical variable able to alter the basal level of circulating miRNAs, and these alterations might be considered as potentially misleading the analytical output.
Highlights
MicroRNAs are small non-coding RNA molecules (18–22 nucleotides in length), actively regulating gene expression [1,2]
Many studies have demonstrated that regular physical activity (PA) reduces the global risk of developing a cancer as well as improves prognosis and reduces the risk of metastasis and side effects of the therapy in subjects treated for primitive tumor [17,94,95]
The main question this study aimed to address is whether physical active status may represent a modifier of the baseline circulating miRNA profile and, may act as a pre-analytical variable that affect the diagnostic potential of miRNAs associated with cancer
Summary
MicroRNAs (miRNAs) are small non-coding RNA molecules (18–22 nucleotides in length), actively regulating gene expression [1,2]. Several miRNAs display a certain degree of cell- or tissue-specificity, while others are more broadly expressed [3]. Circulating miRNAs levels are very low and, much lower than in the tissue/cells source [6], they give particular advantage in the case of tissues hardly subjectable to bioptic procedures (e.g., bone and cartilage) [7,8] and/or to serial monitoring the progress of diseases, such as osteoporosis, fracture risk [9] and tumors [10], as well as the response to physical activity [11,12]. Altered circulating miRNA profiles have been associated with transformation and tumor growth, progression, metastasis and development of drug resistance
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