Analysis of EGFR signaling pathway; miRNAs and inflammatory biomarkers in a high-risk oral cancer population in Pakistan

Oral cancer has high morbidity rates in the Asian region, specifically
Pakistan. However, little insight is available regarding the molecular
pathogenesis and inflammatory biomarkers of this preventable cancer. This
study determined the association of EGFR, NFκB, COX-2, and miRNAs
expression with the chewing habits and high-risk human papillomavirus
(HR-HPV) infection in oral cancer patients.**** Formalin-fixed embedded
blocks (FFPPE) (n=50) were analyzed for transcriptional expression of
EGFR, NFκB, and COX-2 by qPCR, and COX-2 protein expression was checked by
immunohistochemistry (IHC). Array profiling of ~2500 miRNAs was performed
on nine samples, and five miRNAs were selected for validation from this
profiling data. Appropriate statistical tests were applied to check the
association of EGFR., NFκB, COX-2, and miRNAs with chewing and HR-HPV
status, (p<0.05 and 95% CI).**** Of the 50 samples, transcriptional
expression of EGFR was observed in 13 (26%), NFκB in 11 (22%), and COX-2
in 17 (34%) samples, and the majority were chewers. EGFR and COX-2
expression were significantly associated with chewing gutka (the most
carcinogenic form of chewing substance). A total of 281 miRNAs were
dysregulated in miRNA profiling, and in validation, miR 222-3p was
significantly downregulated in chewers expressing EGFR, NFκB, and COX-2
compared to non-chewers (p<0.05). HR-HPV positivity was not
correlated with miRNAs. This study suggests a significant association of
chewing habits with EGFR and COX-2 expression. In addition, the molecular
pathogenesis of OSCC suggests the substantial interplay of NFκB, COX-2,
EGFR and miRNAs in chronic chewers, irrespective of HR-HPV involvement.