A Pan-omics Systems Biology Perspective Identifies Calcium Signaling Pathway Critical in Medullary Thyroid Cancer

Background : Medullary thyroid carcinoma (MTC) is an uncommon type of thyroid cancer that occurs in the thyroid gland's parafollicular C cell. The pan-omics approach aids in determining the molecular pathways and elements important to MTC carcinogenesis. Methodology : SNPs associated with medullary thyroid carcinoma (MTC) were extracted from the DisGeNET database, while differentially expressed genes were obtained from the Gene Expression Omnibus (GEO). Proteomic and metabolomic datasets were retrieved from published studies available in the EMBL-EBI database. The functional implications of the SNPs; and the pathways and gene ontology analysis of SNPs, differentially expressed genes (DEGs), proteins (DEPs), and metabolites (DEMs) were performed. Important kinases and transcription factors (TFs) were also found. To identify the core dysregulated pathways in MTC carcinogenesis, an integrated approach was employed to study the pan-omics data. Results: Calcium signaling pathway was identified as the core dysregulated pathway in MTC. The parent pathways linked with MTC oncogenesis were metabolism, signal transduction, apoptosis, disease, cancer, and cell–extracellular matrix (ECM) interaction and adhesion. Fourteen TFs and eighty-seven kinases that are essential for the development and progression of MTC were identified by the commonality analysis. The core pathway, TFs, and kinases were influential on the clinical outputs like proliferation, metastasis, angiogenesis, EMT, and apoptosis in MTC. Conclusion - The core deregulated pathway, TFs, and kinases deciphered may help identify potential biomarkers and druggable targets for improved patient care and management in MTC.