NGS-based miRNome identifies miR-449 cluster as marker of malignant transformation of sinonasal inverted papilloma

Objective: identification of the miRNA expression profile in sinonasal inverted papilloma (SNIP) as a tool to evaluate the risk of transformation into sinonasal squamous cell carcinoma (SNSCC). Materials and Methods: paired tumour tissues and adjacent normal tissues were obtained from SNIP and SNSCC patients who had undergone surgical resection and used for next-generation sequencing (NGS)-based miRNome analysis. SNIP tissues with concomitant dysplasia (SNIP-DISP) were used as malignant transition samples. By comparing the deregulated miRNAs in SNIP and SNSCC, an miRNA cluster was identified and its physio-and clinical-pathological value was predicted. Results: NGS identified 54 miRNAs significantly down-and upregulated in SNIP. Among them, the miR-449 cluster was upregulated in SNIP and could differentiate the benign tumour from normal tissue. Notably, the miR-449 cluster was found to be significantly underexpressed in SNSCC, and the cluster markedly changed in SNIP during the malignant transition into SNSCC. miRNA enrichment analysis and GO analysis revealed that miR-449 is involved in apoptotic and cell proliferation pathways. Conclusions: Our findings suggest that miR-449 may be involved in the molecular pathogenesis of SNIP and its malignant transformation into SNSCC. miR-449 might therefore be a useful tumour biomarker in patients with SNIP and may also have the potential to be used as a tool for detecting and monitoring the course of the possible malignant transformation.