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HPV related deregulation of selected microRNAs in sinonasal squamous cell carcinoma

Publication at First Faculty of Medicine, Faculty of Medicine in Hradec Králové |
2019

Abstract

Objective: In the present study, we used quantitative real-time PCR to investigate relative expression values of miR-145-5p, miR-484 and miR-99a-5p in HPV positive and HPV negative samples of sinonasal squamous cell carcinoma. Design: Original Article.

Settings: Institute of Clinical Biochemistry and Diagnostics, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Sokolská 581, 500 05 Hradec Králové Materials and Methods: Quantitative real time PCR with TaqManTM Advanced miRNA Assays was used to investigate relative expression values of selected microRNAs (miR-145-5p, miR-484 and miR-99a-5p) in a unique set of formalin-fixed paraffin-embedded tissue samples obtained from 46 patients with sinonasal squamous cell carcinoma. Statistical analysis (Student's t-test, one-way analysis of variance and regression analysis) was performed to compare relative expression miRNA values and recorded clinicopathological data such as HPV status.

Results: Our results show statistically significant downregulation of miR-145-5p (P < 0.001 and Fold change = -2.78) in sinonasal squamous cell carcinoma samples. The presence of HPV infection correlated with the expression levels of all three studied miRNAs.

The expression of miR-145-5p was lower in HPV negative samples (P = 0.019), miR-99a-5p was upregulated in HPV positive samples (P = 0.058) and miR-484 was downregulated in HPV positive samples (P = 0.016). Patients with recorded history of smoking or currents smokers showed downregulation of miR 99a-5p (P = 0.060).

Perineural invasion was linked to significant downregulation of miR-99a-5p (P = 0.0055). Distinctive downregulation of miR-145-5p was linked to vascular invasion (P = 0.037) and regional recurrence (P = 0.076).

Conclusion: We have found correlation between studied miRNA expression and presence of HPV infection in the patient samples. Our results suggest that miR-145, miR-484 and miR-99a are involved in HPV pathogenesis.

However, the actual pathway of HPV related miRNA involvement in sinonasal tumor development is not yet known.