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Network-Based Genetic Profiling Reveals Cellular Pathway Differences Between Follicular Thyroid Carcinoma and Follicular Thyroid Adenoma

Author

Listed:
  • Md. Ali Hossain

    (Department of Computer Science & Engineering, Manarat International University, Khagan, Dhaka 1343, Bangladesh
    These authors contributed equally to this work.)

  • Tania Akter Asa

    (Electrical and Electronic Engineering, Islamic University, Kushtia 7005, Bangladesh
    These authors contributed equally to this work.)

  • Md. Mijanur Rahman

    (Computer Science & Engineering, Jatiya Kabi Kazi Nazrul Islam University, Mymensingh 2205, Bangladesh)

  • Shahadat Uddin

    (Complex Systems Research Group & Project Management Program, Faculty of Engineering, The University of Sydney, Sydney, NSW 2006, Australia)

  • Ahmed A. Moustafa

    (Marcs Institute for Brain and Behaviour and School of Psychology, Western Sydney University, Sydney, NSW 2751, Australia)

  • Julian M. W. Quinn

    (Bone Biology Divisions, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia)

  • Mohammad Ali Moni

    (Bone Biology Divisions, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
    WHO Collaborating Centre on eHealth, School of Public Health and Community Medicine, Faculty of Medicine, The University of New South Wales, Sydney, NSW 2052, Australia)

Abstract

Molecular mechanisms underlying the pathogenesis and progression of malignant thyroid cancers, such as follicular thyroid carcinomas (FTCs), and how these differ from benign thyroid lesions, are poorly understood. In this study, we employed network-based integrative analyses of FTC and benign follicular thyroid adenoma (FTA) lesion transcriptomes to identify key genes and pathways that differ between them. We first analysed a microarray gene expression dataset (Gene Expression Omnibus GSE82208, n = 52) obtained from FTC and FTA tissues to identify differentially expressed genes (DEGs). Pathway analyses of these DEGs were then performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) resources to identify potentially important pathways, and protein-protein interactions (PPIs) were examined to identify pathway hub genes. Our data analysis identified 598 DEGs, 133 genes with higher and 465 genes with lower expression in FTCs. We identified four significant pathways (one carbon pool by folate, p53 signalling, progesterone-mediated oocyte maturation signalling, and cell cycle pathways) connected to DEGs with high FTC expression; eight pathways were connected to DEGs with lower relative FTC expression. Ten GO groups were significantly connected with FTC-high expression DEGs and 80 with low-FTC expression DEGs. PPI analysis then identified 12 potential hub genes based on degree and betweenness centrality; namely, TOP2A, JUN, EGFR, CDK1, FOS, CDKN3, EZH2, TYMS, PBK, CDH1, UBE2C, and CCNB2. Moreover, transcription factors (TFs) were identified that may underlie gene expression differences observed between FTC and FTA, including FOXC1, GATA2, YY1, FOXL1, E2F1, NFIC, SRF, TFAP2A, HINFP, and CREB1. We also identified microRNA (miRNAs) that may also affect transcript levels of DEGs; these included hsa-mir-335-5p, -26b-5p, -124-3p, -16-5p, -192-5p, -1-3p, -17-5p, -92a-3p, -215-5p, and -20a-5p. Thus, our study identified DEGs, molecular pathways, TFs, and miRNAs that reflect molecular mechanisms that differ between FTC and benign FTA. Given the general similarities of these lesions and common tissue origin, some of these differences may reflect malignant progression potential, and include useful candidate biomarkers for FTC and identifying factors important for FTC pathogenesis.

Suggested Citation

  • Md. Ali Hossain & Tania Akter Asa & Md. Mijanur Rahman & Shahadat Uddin & Ahmed A. Moustafa & Julian M. W. Quinn & Mohammad Ali Moni, 2020. "Network-Based Genetic Profiling Reveals Cellular Pathway Differences Between Follicular Thyroid Carcinoma and Follicular Thyroid Adenoma," IJERPH, MDPI, vol. 17(4), pages 1-21, February.
  • Handle: RePEc:gam:jijerp:v:17:y:2020:i:4:p:1373-:d:323129
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