MicroRNA Signatures Associated with Basal Cell Carcinoma Subtypes

Basal cell carcinoma (BCC) is classified histologically into subtypes that determine treatment decisions. Micro RNAs (miRs) are short non-coding RNAs that may serve as diagnostic biomarkers. We investigated if particular miRs could distinguish BCC subtypes. We sequenced miRs from 55 archival BCC and 9 control skin specimens, and then validated these miRs by qRT-PCR assay on a second BCC cohort (18 superficial, 16 nodular, 15 infiltrative) and control skin (n= 12). Expression values for individual miRs were normalized to miR-16-5p, which was least variant among the control skin and BCC samples. We found that 1) miR-383-5p and miR-145-5p are downregulated in all BCC subtypes compared to control skin, 2) miR-181c-5p is downregulated in superficial compared to invasive (nodular/infiltrative) BCC, and 3) miR-22-5p and miR-708-5p are upregulated in infiltrative compared to superficial/nodular BCC and miR-30c-5p is downregulated in infiltrative compared to nodular BCC. Receiver operating characteristic analysis demonstrated excellent capacity of these miRs to discriminate between BCC and control skin (area under curve 0.94-0.98), while capacity to discriminate between superficial and invasive subtypes was less robust (area under curves 0.7-0.8). Future prospective studies may determine the utility of these miRs as diagnostic biomarkers to guide biopsy and treatment of BCC.