Molecular pathogenisis of papillary thyroid carcinoma

Thyroid cancer is the top endocrine malignancy and second most common female malignancy in the United Arab Emirates. Due to the fact that thyroid cancer is a rare disease, only a few studies have investigated the molecular pathogenesis of the disease worldwide, with no studies for the UAE populations. To our knowledge, this study is the first to provide an insight into the molecular pathogenesis of papillary thyroid cancer (PTC) in UAE. In order to do so, first an epidemiological study was conducted on data collected from local and international platforms showed a steady increase in thyroid cancer incidence in UAE and worldwide. Thyroid cancer was also found to be a female malignancy affecting (35 – 39 years old) group more. Second, an in silico analysis study was performed using bioinformatics techniques on publicly available transcriptomic studies of selected populations revealed several activated pathways most importantly, MAPK pathway which was activated across different stages of PTC. The study also showed that KCNQ1, CACNA1D, KCNN4 , EGFR and PTK2B genes were associated with PTC progression. In vivo-validation of these genes using UAE-clinical biopsies showed more enrichment in metastatic stage of PTC. Third, a whole transcriptomic analysis was performed using next-generation sequencing on UAE clinical biopsies also revealed MAPK pathway (MAPK6) involvement in PTC progression. Additional validation by genomic transfection of MAPK6 into thyroid cell lines followed by transcriptomic analysis revealed the putative role of (MAPK6, HIST3H3, TLX3, ADAM9, OGT, GREB1) gens and (estrogen, vitamin D )pathways in driving PTC progression. Furthermore, the Drug bank database related to expressed genes identified a variety of FDA-approved drugs that are currently being used to treat other medical conditions and may be useful in treating thyroid carcinoma. To sum, The primary oncogenic machinery that drives thyroid carcinogenesis constitutes a cooperation and close connection of cellular pathways such as MAPK, PI3K, VEGF, vitamin D, and estrogen, which are centrally driven by altered components. Therefore, a clearer understanding of the underlying mechanisms and drivers of TC pathogenesis may lead to promising opportunities for novel drug discoveries and clinical strategies for treatment and management.