The Relationship of Grade, Stage and Tobacco Usage in Head and Neck Squamous Cell Carcinoma With p53, PIK3CA and MicroRNA Profiles

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) has multiple epigenetic modifications including post-transcriptional regulation by microRNAs (miRNAs) as well as alterations in molecular pathways due to mutations. Examining these miRNAs and location-specific molecular alterations is essential to understanding the intricacies of HNSCC and directing focused diagnoses and treatments. Aim: To investigate tobacco-related changes in the expression of miRNAs and proteins with clinicopathological parameters of HNSCC and disease-modifying personal habits like tobacco and alcohol use. Methodology: The study concentrated on oropharyngeal cancers using immunohistochemistry and reverse transcription-polymerase chain reaction. Expression of microRNAs mir15a, mir20b, mir21, mir31, mir33b, mir146a, mir155, mir218, mir363 and mir497 and immunohistochemical expression of P53 and PIK3CA were correlated with grade, stage and personal habits like tobacco and alcohol intake. Results: mir21 and mir15a are under-expressed in higher grades with a trend towards statistical significance (P-value of 0.094 and 0.056 by one-way analysis of variance (ANOVA) on ΔC T values). mir155 and mir146a are overexpressed in stage IV tumours while mir 31 is under-expressed in stage IV tumours but statistical significance was not reached. mir497 showed overexpression in tobacco users, but these results were limited by many tumours not showing any amplification for the miRNA and statistical significance was not reached. There was no statistically significant association found between immunohistochemical expression of p53 and PIK3CA with grade, stage or personal habits. Conclusion: Through the deciphering of complex miRNA patterns and their relationships with clinicopathology, this study attempted to increase our understanding of HNSCC. Some candidate miRNAs showing probable association with grade, stage and personal habits were identified, but larger studies are needed to confirm or refute the importance of these miRNAs.