Almansoori, Asma;
Bhamidimarri, Poorna Manasa;
Bendardaf, Riyad;
Hamoudi, Rifat;
(2022)
In silico Analysis of Publicly Available Transcriptomics Data Identifies Putative Prognostic and Therapeutic Molecular Targets for Papillary Thyroid Carcinoma.
International Journal of General Medicine
, 2022
(15)
pp. 3097-3120.
10.2147/IJGM.S345336.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | In silico Analysis of Publicly Available Transcriptomics Data Identifies Putative Prognostic and Therapeutic Molecular Targets for Papillary Thyroid Carcinoma |
| Location: | New Zealand |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.2147/IJGM.S345336 |
| Publisher version: | https://doi.org/10.2147/IJGM.S345336 |
| Language: | English |
| Additional information: | © 2022 Almansoori et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/ terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Medicine, General & Internal, General & Internal Medicine, thyroid cancer, BIG data analytics, absolute GSEA, pathway analysis, pharmacotranscriptomics, RNAseq, FFPE clinical biopsies, TYROSINE KINASE INHIBITOR, DOUBLE-BLIND, POTASSIUM CHANNELS, CANCER, CABOZANTINIB, VANDETANIB, EXPRESSION, MUTATIONS, GENE, GROWTH |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10148926 |
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