{"title":"Prioritization of drug targets for thyroid cancer: a multi-omics Mendelian randomization study.","authors":"Hong Sun, Ling Li, Jingchao Yan, Taomin Huang","doi":"10.1007/s12020-024-03933-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Recurrence or tumor metastasis and drug resistance remain the major challenge in the treatment of thyroid cancer. It is needed to identify novel drug targets for thyroid cancer.</p><p><strong>Methods: </strong>Summary data-based Mendelian randomization (SMR) and colocalization analysis were performed to evaluate the associations between gene methylation, expression, protein levels with thyroid cancer. We additionally performed protein-protein interaction (PPI) network, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses to further explore the potential roles of identified genes in thyroid cancer.</p><p><strong>Results: </strong>SDCCAG8 and VCAM1 genes were associated with risk of thyroid cancer with tier 1 evidence, while TCN2 gene was with tier 3 evidence. SDCCAG8 gene was associated with risk of papillary thyroid cancer with tier 1 evidence. At the level of circulating proteins, genetically predicted higher levels of SDCCAG8 (OR = 0.46, 95% CI 0.34-0.64) and VCAM1 (OR = 0.21, 95% CI 0.10-0.45) were inversely associated with thyroid cancer risk; higher level of TCN2 was associated with an increased risk of thyroid cancer (OR = 1.30, 95% CI 1.15-1.47); and the higher level of SDCCAG8 (OR = 0.40, 95% CI 0.28-0.58) was associated with a decreased risk of papillary thyroid cancer. The bioinformatics analysis showed that SDCCAG8, VCAM1 and TCN2 might play roles in immune-related pathways.</p><p><strong>Conclusion: </strong>SDCCAG8, VCAM1 and TCN2 genes were associated with thyroid cancer risk with evidence at multi-omics levels. There were potential roles of SDCCAG8, VCAM1 and TCN2 in immune-related pathways. Our findings might improve the understanding of the pathogenesis of thyroid cancer and discovery of novel potential drug targets for this disease.</p>","PeriodicalId":11572,"journal":{"name":"Endocrine","volume":" ","pages":"732-743"},"PeriodicalIF":3.7000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12020-024-03933-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/19 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: Recurrence or tumor metastasis and drug resistance remain the major challenge in the treatment of thyroid cancer. It is needed to identify novel drug targets for thyroid cancer.
Methods: Summary data-based Mendelian randomization (SMR) and colocalization analysis were performed to evaluate the associations between gene methylation, expression, protein levels with thyroid cancer. We additionally performed protein-protein interaction (PPI) network, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses to further explore the potential roles of identified genes in thyroid cancer.
Results: SDCCAG8 and VCAM1 genes were associated with risk of thyroid cancer with tier 1 evidence, while TCN2 gene was with tier 3 evidence. SDCCAG8 gene was associated with risk of papillary thyroid cancer with tier 1 evidence. At the level of circulating proteins, genetically predicted higher levels of SDCCAG8 (OR = 0.46, 95% CI 0.34-0.64) and VCAM1 (OR = 0.21, 95% CI 0.10-0.45) were inversely associated with thyroid cancer risk; higher level of TCN2 was associated with an increased risk of thyroid cancer (OR = 1.30, 95% CI 1.15-1.47); and the higher level of SDCCAG8 (OR = 0.40, 95% CI 0.28-0.58) was associated with a decreased risk of papillary thyroid cancer. The bioinformatics analysis showed that SDCCAG8, VCAM1 and TCN2 might play roles in immune-related pathways.
Conclusion: SDCCAG8, VCAM1 and TCN2 genes were associated with thyroid cancer risk with evidence at multi-omics levels. There were potential roles of SDCCAG8, VCAM1 and TCN2 in immune-related pathways. Our findings might improve the understanding of the pathogenesis of thyroid cancer and discovery of novel potential drug targets for this disease.
目的：复发或肿瘤转移以及耐药性仍然是甲状腺癌治疗的主要挑战。我们需要找到治疗甲状腺癌的新药靶点：方法：我们进行了基于数据摘要的孟德尔随机化（SMR）和共定位分析，以评估基因甲基化、表达、蛋白水平与甲状腺癌之间的关联。此外，我们还进行了蛋白-蛋白相互作用（PPI）网络、基因本体（GO）和京都基因与基因组百科全书（KEGG）分析，以进一步探讨已发现基因在甲状腺癌中的潜在作用：结果：SDCCAG8和VCAM1基因与甲状腺癌风险相关，证据等级为一级，而TCN2基因与甲状腺癌风险相关，证据等级为三级。SDCCAG8基因与甲状腺乳头状癌的风险相关，证据为1级。在循环蛋白水平上，遗传预测的较高水平的 SDCCAG8（OR = 0.46，95% CI 0.34-0.64）和 VCAM1（OR = 0.21，95% CI 0.10-0.45）与甲状腺癌的风险成反比。45）与甲状腺癌风险成反比；TCN2水平越高，甲状腺癌风险越高（OR = 1.30，95% CI 1.15-1.47）；SDCCAG8水平越高（OR = 0.40，95% CI 0.28-0.58），甲状腺乳头状癌风险越低。生物信息学分析表明，SDCCAG8、VCAM1和TCN2可能在免疫相关通路中发挥作用：结论：SDCCAG8、VCAM1和TCN2基因与甲状腺癌风险相关，这在多组学水平上都有证据。SDCCAG8、VCAM1和TCN2可能在免疫相关通路中发挥作用。我们的发现可能会加深人们对甲状腺癌发病机制的理解，并发现治疗这种疾病的新的潜在药物靶点。
期刊介绍：
Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology.
Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted.
Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.
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