Investigating the immune-modulatory association of miRNAs in HPV-associated HNSCC individuals: A bioinformatics approach.

Head and Neck Squamous Cell Carcinoma (HNSCC) diagnosis remains a challenge for clinicians, with human papillomavirus (HPV) status long associated with HNSCC prognosis and response to therapy. Small non-coding molecules, such as microRNAs (miRNAs), significantly alter gene expression, particularly of immune-modulatory genes. In the current study, an effort to map the interaction patterns between miRNAs and their target genes was carried out using diverse computational tools. A microarray-based study was retrieved and analysed using GEO2R to identify ubiquitously expressed miRNAs in HPV-associated HNSCC samples, with HPV-negative samples used as controls. Seven miRNAs were identified, namely hsa-miR-150-5p, hsa-miR-142-5p, hsa-miR-142-3p, hsa-miR-1-3p, hsa-miR-133b, hsa-miR-206, and hsa-miR-1260b. Functional annotation using miRNet identified numerous significant signalling pathways dysregulated by the aforementioned miRNAs. miRDB was used to map miRNA target genes, which were visualised in Cytoscape; among these, key immune-modulatory genes were analysed in a comprehensive meta-analysis. Furthermore, the GEPIA2 tool was used to perform survival analysis and generate Kaplan-Meier plots correlating survival percentages in HNSCC patients with gene expression patterns. The viral infectious cycle was dysregulated by miR-1260b expression. DKK1, STC2, SPOCK1, and TP53 were among the genes whose aberrant expression was associated with a significant reduction in survival in HNSCC-affected individuals. This report elucidates the pivotal role of miRNAs in modulating the expression of key immune-modulatory genes, thereby influencing the prognosis of HNSCC and HPV infection.