Skip to Main content Skip to Navigation
Journal articles

Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma

Om Kulkarni 1 Pierre-Emmanuel Sugier 2, 3 Julie Guibon 1, 2, 3 Anne Boland-Augé 4 Christine Lonjou 1 Delphine Bacq-Daian 4 Robert Olaso 4 Carole Rubino 2, 3 Vincent Souchard 2, 3 Frédérique Rachedi Juan Jesus Lence-Anta Rosa Maria Ortiz Constance Xhaard 2, 3, 5, 6, 7, 8 Pierre Laurent-Puig 9 Claire Mulot 9 Anne-Valérie Guizard 10, 11 Claire Schvartz 12 Marie-Christine Boutron-Ruault 2, 3 Evgenia Ostroumova 13 Ausrele Kesminiene 13 Jean-François Deleuze 4 Pascal Guénel 2, 3 Florent de Vathaire 2, 3 Thérèse Truong 2, 3 Fabienne Lesueur 1
Abstract : Variants identified in earlier genome-wide association studies (GWAS) on differentiated thyroid carcinoma (DTC) explain about 10% of the overall estimated genetic contribution and could not provide complete insights into biological mechanisms involved in DTC susceptibility. Integrating systems biology information from model organisms, genome-wide expression data from tumor and matched normal tissue and GWAS data could help identifying DTC-associated genes, and pathways or functional networks in which they are involved. We performed data mining of GWAS data of the EPITHYR consortium (1551 cases and 1957 controls) using various pathways and protein-protein interaction (PPI) annotation databases and gene expression data from The Cancer Genome Atlas. We identified eight DTC-associated genes at known loci 2q35 (DIRC3), 8p12 (NRG1), 9q22 (FOXE1, TRMO, HEMGN, ANP32B, NANS) and 14q13 (MBIP). Using the EW_dmGWAS approach we found that gene networks related to glycogenolysis, glycogen metabolism, insulin metabolism and signal transduction pathways associated with muscle contraction were overrepresented with association signals (false discovery rate adjusted p-value < 0.05). Additionally, suggestive association of 21 KEGG and 75 REACTOME pathways with DTC indicate a link between DTC susceptibility and functions related to metabolism of cholesterol, amino sugar and nucleotide sugar metabolism, steroid biosynthesis, and downregulation of ERBB2 signaling pathways. Together, our results provide novel insights into biological mechanisms contributing to DTC risk.
Document type :
Journal articles
Complete list of metadata

https://hal.sorbonne-universite.fr/hal-03243030
Contributor : Hal Sorbonne Université Gestionnaire Connect in order to contact the contributor
Submitted on : Monday, May 31, 2021 - 1:54:38 PM
Last modification on : Wednesday, November 17, 2021 - 12:34:04 PM

File

s41598-021-88253-0.pdf
Publication funded by an institution

Identifiers

Citation

Om Kulkarni, Pierre-Emmanuel Sugier, Julie Guibon, Anne Boland-Augé, Christine Lonjou, et al.. Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma. Scientific Reports, Nature Publishing Group, 2021, 11 (1), pp.8932. ⟨10.1038/s41598-021-88253-0⟩. ⟨hal-03243030⟩

Share

Metrics

Record views

286

Files downloads

201