Abstract
Cutaneous squamous cell carcinoma is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as poor-prognosis diseases, and therefore it is important to identify new markers to better predict its clinical evolution. Here, we identified the expression pattern of miRNAs at different stages of skin cancer progression in a panel of murine skin cancer cell lines. We determined that miR-203 and miR-205 are differentially expressed in this panel, and evaluated their potential use as biomarkers of prognosis in human tumours. MiR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. MiR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. MiR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR-203 and miR-205 expression, and pathological tumour features. This work highlights the utility of miRNA-205 and miRNA-203 as prognostic markers in cutaneous squamous cell carcinoma.
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