Background: Thyroid cancer is the ninth most common malignancy worldwide, but the third most common malignancy in the United Arab Emirates (UAE). To our knowledge, this is the first UAE nationwide study aimed at presenting incidence rates of thyroid cancer at the national level of UAE based upon data from the national cancer registry and GLOBOCAN. Methods: Between 2011 and 2017, a total of 2036 thyroid cancer cases from UAE patients were registered, of which 75.3% were female and 24.7% male patients. Results: The results showed 6.6% increase in thyroid cancer cases in the UAE from 2011 to 2017 (p < 0.001) with a rise of approximately 400 cases per year from 2011 to 2040. Age standardized rate calculations showed increase in prevalence from 1.18 in 2011 to 4.32 in 2017 but decreases in incidence from 1.05 in 2011 to 0.15 in 2017. This trend is confirmed by the predictive model showing increase in incidence from 0.15 in 2017 to 0.64 by 2040. Gender was shown to be significantly associated with thyroid cancer. The female to male ratio was significantly higher in Emirati patients (4.86:1) (p < 0.001) than expat patients (2.47:1) (p < 0.01). Interestingly, expat patients contributed to the majority of thyroid cancer cases despite having lower female to male ratio. The age at diagnosis was significantly associated with thyroid cancer (p = 0.03) with the highest frequency diagnosed at 35-39 years of age. Globally, data from the predictive model showed that Asia had the highest rate of increase per year and UAE the lowest. Conclusions: The slight increase in thyroid cancer prevalence and incidence, together with the different female to male ratio and diagnosis at younger age warrants further investigation at the molecular level from UAE thyroid cancer patients to elucidate the molecular basis of thyroid cancer.
Background Thyroid cancer is the most common endocrine malignancy. However, the molecular mechanism involved in its pathogenesis is not well characterized. Purpose The objective of this study is to identify key cellular pathways and differentially expressed genes along the thyroid cancer pathogenesis sequence as well as to identify potential prognostic and therapeutic targets. Methods Publicly available transcriptomics data comprising a total of 95 samples consisting of 41 normal, 28 non-aggressive and 26 metastatic papillary thyroid carcinoma (PTC) cases were used. Transcriptomics data were normalized and filtered identifying 9394 differentially expressed genes. The genes identified were subjected to pathway analysis using absGSEA identifying PTC related pathways. Three of the genes identified were validated on 508 thyroid cancer biopsies using RNAseq and TNMplot. Results Pathway analysis revealed a total of 2193 differential pathways among non-aggressive samples and 1969 among metastatic samples compared to normal tissue. Pathways for non-aggressive PTC include calcium and potassium ion transport, hormone signaling, protein tyrosine phosphatase activity and protein tyrosine kinase activity. Metastatic pathways include growth, apoptosis, activation of MAPK and regulation of serine threonine kinase activity. Genes for non-aggressive are KCNQ1, CACNA1D, KCNN4, BCL2, and PTK2B and metastatic PTC are EGFR, PTK2B, KCNN4 and BCL2. Three of the genes identified were validated using clinical biopsies showing significant overexpression in aggressive compared to non-aggressive PTC; EGFR (p < 0.05), KCNN4 (p < 0.001) and PTK2B (p < 0.001). DrugBank database search identified several FDA approved drug targets including anti-EGFR Vandetanib used to treat thyroid cancer in addition to others that may prove useful in treating PTC. Conclusion Transcriptomics analysis identified putative prognostic targets including EGFR, PTK2B, BCL2, KCNQ1, KCNN4 and CACNA1D. EGFR, PTK2B and KCN44 were validated using thyroid cancer clinical biopsies. The drug search identified FDA approved drugs including Vandetanib in addition to others that may prove useful in treating the disease.
Background: Thyroid cancer is the ninth most common malignancy worldwide, but the third most common malignancy in the United Arab Emirates (UAE). To our knowledge, this is the first UAE nationwide study aimed at presenting incidence rates of thyroid cancer at the national level of UAE based upon data from the national cancer registry and GLOBOCAN. Methods: Between 2011 and 2017, a total of 2036 thyroid cancer cases from UAE patients were registered, of which 75.3% were female and 24.7% male patients. Results: The results showed 6.6% increase in thyroid cancer cases in the UAE from 2011 to 2017 (p < 0.001) with a rise of approximately 400 cases per year from 2011 to 2040. Age standardized rate calculations showed increase in prevalence from 1.18 in 2011 to 4.32 in 2017 but decreases in incidence from 1.05 in 2011 to 0.15 in 2017. This trend is confirmed by the predictive model showing increase in incidence from 0.15 in 2017 to 0.64 by 2040. Gender was shown to be significantly associated with thyroid cancer. The female to male ratio was significantly higher in Emirati patients (4.86:1) (p < 0.001) than expat patients (2.47:1) (p < 0.01). Interestingly, expat patients contributed to the majority of thyroid cancer cases despite having lower female to male ratio. The age at diagnosis was significantly associated with thyroid cancer (p = 0.03) with the highest frequency diagnosed at 35-39 years of age. Globally, data from the predictive model showed that Asia had the highest rate of increase per year and UAE the lowest. Conclusions: The slight increase in thyroid cancer prevalence and incidence, together with the different female to male ratio and diagnosis at younger age warrants further investigation at the molecular level from UAE thyroid cancer patients to elucidate the molecular basis of thyroid cancer.
Thyroid Cancer is the most common endocrine malignancy. Although the mortality rate of thyroid cancer is considered to be low, however the reoccurrence and persistence of the disease is still considered high. The most common type of thyroid cancer is papillary thyroid carcinoma consisting of >70% of all types of thyroid cancer. Thyroid cancer is heterogeneous and complex. BIG data in the form of publicly available gene expression (transcriptomics) datasets can provide valuable source to gain deeper understanding of complex diseases such as papillary thyroid carcinoma (PTC). In this study, we used a novel bioinformatics method based on adaptive filtering to reduce the number of genes expressed eliminating genes that are invariant across the various disease stages. In order to shed light on some of the mechanisms involved in PTC, the filtered genes were used in systematic pathway analysis searches across 20,500 annotated cellular pathways using modified Kolmogorov-Smirnov algorithm to identify the relevant differentially activated cellular pathways across the various stages of the disease. Our analysis from 95 PTC patient biopsies consisting of 41 normal, 28 nonaggressive and 26 metastatic papillary thyroid carcinoma revealed 2193 differential activated cellular pathways among non-aggressive samples and 1969 among metastatic samples compared to normal tissue. The key pathways for non-aggressive PTC includes calcium and potassium ion transport, hormone signaling pathways, protein tyrosine phosphatase activity and protein tyrosine kinase activity. The key pathways for metastatic PTC include growth, apoptosis, activation of MAPK activity and regulation of serine threonine kinase activity. The most frequent genes across the enriched pathways were KCNQ1, CACNA1D, KCNN4, BCL2, and PTK2B for non-aggressive PTC, and EGFR, PTK2B, KCNN4 and BCL2 for metastatic PTC. Survival analysis results showed that PTK2B, CACNA1D and BCL2 contributed to poor survival of PTC patients. The study identified insights into mechanisms of PTC.
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