Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma.
Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma.
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DOI：
10.1038/s41598-021-88253-0
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发表时间：
2021-04-26
影响因子：
4.6
通讯作者：
Lesueur F
中科院分区：
文献类型：
--
作者：
Kulkarni O;Sugier PE;Guibon J;Boland-Augé A;Lonjou C;Bacq-Daian D;Olaso R;Rubino C;Souchard V;Rachedi F;Lence-Anta JJ;Ortiz RM;Xhaard C;Laurent-Puig P;Mulot C;Guizard AV;Schvartz C;Boutron-Ruault MC;Ostroumova E;Kesminiene A;Deleuze JF;Guénel P;De Vathaire F;Truong T;Lesueur F
在早期分化型甲状腺癌（DTC）的全基因组关联研究（GWAS）中发现的变异解释了约10%的总体估计遗传贡献，并且不能提供对DTC易感性所涉及的生物学机制的完整见解。整合来自模式生物的系统生物学信息，来自肿瘤和匹配的正常组织的全基因组表达数据以及GWAS数据可以帮助识别DTC相关基因，以及它们参与的途径或功能网络。我们使用各种途径和蛋白质-蛋白质相互作用（PPI）注释数据库以及来自癌症基因组图谱的基因表达数据，对EPITHYR联盟的GWAS数据（1551例病例和1957例对照）进行数据挖掘。我们在2 q35（DIRC 3）、8 p12（NRG 1）、9 q22（FOXE 1、TRMO、HEGN、ANP 32 B、NANS）和14 q13（MBIP）基因座上鉴定了8个DTC相关基因。使用EW_dmGWAS方法，我们发现与糖原分解、糖原代谢、胰岛素代谢和与肌肉收缩相关的信号转导途径相关的基因网络被关联信号过度表示（假发现率调整的p值< 0.05）。此外，21 KEGG和75 REACTOME通路与DTC的暗示性关联表明DTC易感性与胆固醇代谢、氨基糖和核苷酸糖代谢、类固醇生物合成和ERBB 2信号通路下调相关的功能之间存在联系。总之，我们的研究结果为DTC风险的生物学机制提供了新的见解。
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.
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影响因子：
--
作者：
Das J;Yu H
通讯作者：
Yu H
影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
影响因子：
5.8
作者：
Kohler, Aleksandra;Chen, Bowang;Forsti, Asta
通讯作者：
Forsti, Asta
影响因子：
6.4
作者：
Hemminki, K;Lit, XJ
通讯作者：
Lit, XJ
DOI：
10.1158/1055-9965.epi-16-0106
发表时间：
2017-01
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Amos CI;Dennis J;Wang Z;Byun J;Schumacher FR;Gayther SA;Casey G;Hunter DJ;Sellers TA;Gruber SB;Dunning AM;Michailidou K;Fachal L;Doheny K;Spurdle AB;Li Y;Xiao X;Romm J;Pugh E;Coetzee GA;Hazelett DJ;Bojesen SE;Caga-Anan C;Haiman CA;Kamal A;Luccarini C;Tessier D;Vincent D;Bacot F;Van Den Berg DJ;Nelson S;Demetriades S;Goldgar DE;Couch FJ;Forman JL;Giles GG;Conti DV;Bickeböller H;Risch A;Waldenberger M;Brüske-Hohlfeld I;Hicks BD;Ling H;McGuffog L;Lee A;Kuchenbaecker K;Soucy P;Manz J;Cunningham JM;Butterbach K;Kote-Jarai Z;Kraft P;FitzGerald L;Lindström S;Adams M;McKay JD;Phelan CM;Benlloch S;Kelemen LE;Brennan P;Riggan M;O'Mara TA;Shen H;Shi Y;Thompson DJ;Goodman MT;Nielsen SF;Berchuck A;Laboissiere S;Schmit SL;Shelford T;Edlund CK;Taylor JA;Field JK;Park SK;Offit K;Thomassen M;Schmutzler R;Ottini L;Hung RJ;Marchini J;Amin Al Olama A;Peters U;Eeles RA;Seldin MF;Gillanders E;Seminara D;Antoniou AC;Pharoah PD;Chenevix-Trench G;Chanock SJ;Simard J;Easton DF
通讯作者：
Easton DF