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Differentially expressed miRNAs in fresh tumour samples distinguishes HPV positive and HPV negative HNSCC

Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common malignancy worldwide. Based on the etiology, HNSCC can be divided into two distinctive major groups: 1) human papillomavirus positive (HPV+) tumours that are mostly found in younger population, rarely linked with TP53 mutations, often of oropharyngeal origin and associated with better response to treatment ; and 2) HPV negative (HPV-) tumours that are associated with heavy smoking and/or drinking, older age, with TP53 mutations, with no preferential anatomical location, and with poor prognosis (Slebos et al, 2006). Treatment options for both patient groups involve radiotherapy, surgery, chemotherapy and biological therapy or a combination of modalities. However, due to the different prognosis of patients it seems plausible to individualize the treatment based on the cause of the malignancy (Fakhry et al, 2008). Therefore, it is crucial to identify more sensitive and specific epigenetic biomarkers (i.e. miRNAs) and to further investigate HPV association with HNSCC. It is well known that deregulation of miRNAs is associated with almost all human malignancies and recent studies showed several differentially expressed miRNAs in HPV+ and HPV- HNSCC (Lajer et al, 2012 ; Gao et al, 2013 ; Vojtechova et al, 2016 ; Spence et al, 2016). We therefore investigated miRNA profile of HPV+HNSCC tumours, HPV-tumours and of non- malignant tonsils (normal controls). Seven HPV+ HNSCC, 12 HPV- HNSCC patient samples and 3 normal controls have been included in the study. The miRNAseq analysis (Illumina) determined several differentially expressed miRNAs (miRNA-21, -31, -26b, -101) in tumour tissues compared to controls, as in HPV+ tumours compared to HPV- tumours (miRNA-34a, -363, -106, -20b), which are consistent with the literature. The expressions of these significantly deregulated miRNAs will be confirmed by Q-RT-PCR. In conclusion, the identified miRNAs represent potential specific new prognostic and diagnostic biomarkers, and possibly therapeutic target.

HNSCC, HPV, Oropharinx, microRNA, epigenetic biomarkers

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