Dataset Information

Network-Based Analysis Reveals Association of FOXE1 Gene Polymorphisms in Thyroid Cancer Patients; A Case-Control Study in Southeast of Iran.

ABSTRACT: Thyroid cancer (TC) is the mainly frequent endocrine cancer by different incidence rate in worldwide. However, early prediction of this cancer is still challenging due to the unclear pathogenicity. In this study with the aid of systems biology approach, performed a holistic study on GSE65144 dataset containing anaplastic thyroid carcinoma tissues. Co-expression network analysis by WGCNA suggested that highly preserved turquoise module with 1,480 genes was significantly correlated to TC. Most of the top 54 hub-genes of this module are functionality correlated to thyroid hormone generation (GO:0006590). Of these 54 hub-genes, FOXE1 has been reported previously to contain mutation asosiated to TC and chosen for experimental validation step. To this end, we conducted a case-control study including 81 TC patients and 165 controls individuals to evaluate the effects of FOXE1 functional polymorphisms (rs1867277) on the development of TC in Sistan and Balouchestan province of Iran. The polymorphisms of FOXE1 gene (rs1867277) assessed by tetra-ARMS PCR technique. Homozygous (GG) and (AA) variant of rs1867277 polymorphism were detected in 26 (32.1%) and 15 (18.5 %) of TC patients, and 66 (40.0%), and 15 (9.1%) in controls, respectively (p-value= 0.03, OR= 2.53). The A allele frequency was 70 (43.2%) in TC patients and 114 (34.5%) in controls (p-value= 0.06, OR= 1.44). Overall, our results suggested that FOXE1 gene could be used as a prognostic marker in TC and also provides information related to FOXE1 functional polymorphisms (rs1867277) in Sistan and Balouchestan province of Iran.
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SUBMITTER: Mehrazin A

PROVIDER: S-EPMC7779442 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Network-Based Analysis Reveals Association of FOXE1 Gene Polymorphisms in Thyroid Cancer Patients; A Case-Control Study in Southeast of Iran.

Mehrazin Ahmad A Safarpour Hossein H Davoudi Seyedeh Tahmineh ST Parsamanesh Negin N Saeedi Farhad F Miri-Moghaddam Ebrahim E

Asian Pacific journal of cancer prevention : APJCP 20200901 9

Thyroid cancer (TC) is the mainly frequent endocrine cancer by different incidence rate in worldwide. However, early prediction of this cancer is still challenging due to the unclear pathogenicity. In this study with the aid of systems biology approach, performed a holistic study on GSE65144 dataset containing anaplastic thyroid carcinoma tissues. Co-expression network analysis by WGCNA suggested that highly preserved turquoise module with 1,480 genes was significantly correlated to TC. Most of ...[more]

PMID: 32986379

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Project description:BackgroundFoxE1 is a thyroid-specific forkhead transcription factor essential for thyroid gland development, as well as for the maintenance of the thyroid differentiated state in adults. FoxE1 recognizes and binds to a short DNA sequence present in thyroglobulin (Tg) and thyroperoxidase (Tpo) promoters, but FoxE1 binding to regulatory regions other than Tg and Tpo promoters remains almost unexplored. Improving knowledge of the regulatory functions of FoxE1 is necessary to clarify its role in endocrine syndromes and cancer susceptibility.Methodology/principal findingIn order to further investigate downstream FoxE1 targets, we performed a genome-wide expression screening after knocking-down FoxE1 and obtained new insights into FoxE1 transcriptional networks in thyroid follicular cells. After validation, we confirmed Adamts9, Cdh1, Duox2 and S100a4 as upregulated genes and Casp4, Creld2, Dusp5, Etv5, Hsp5a, Nr4a2 and Tm4sf1 as downregulated genes when FoxE1 was silenced. In promoter regions of putative FoxE1-regulated genes and also in the promoters of the classical thyroid genes Nis, Pax8 and Titf1, we performed an in silico search of the FoxE1 binding motif that was in close proximity to the NF1/CTF binding sequence, as previously described for other forkhead factors. Using chromatin immunoprecipitation we detected specific in vivo FoxE1 binding to novel regulatory regions in two relevant thyroid genes, Nis and Duox2. Moreover, we demonstrated simultaneous binding of FoxE1 and NF1/CTF to the Nis upstream enhancer region, as well as a clear functional activation of the Nis promoter by both transcription factors.Conclusions/significanceIn search for potential downstream mediators of FoxE1 function in thyroid cells, we identified two novel direct FoxE1 target genes. To our knowledge, this is the first evidence regarding the implication of Nis and Duox2 in executing the transcriptional program triggered by FoxE1. Furthermore, this study points out the important role of FoxE1 in the regulation of a large number of genes in thyroid cells.

Project description:BackgroundRecent researches suggest that the CD160/HVEM/LIGHT/BTLA signaling pathway may contribute to the pathogeneses of autoimmune diseases, but the relationship between CD160 polymorphisms and autoimmune thyroid disease (AITD) has not been reported yet. This study aimed to evaluate the associations between CD160 polymorphisms and AITD.MethodsA total of 1017 patients with AITD (634 Graves' disease and 383 Hashimoto's thyroiditis) and 856 unrelated healthy controls were recruited into our study. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated through logistic regression analyses. The CD160 SNPs were detected using Hi-SNP high-throughput genotyping.ResultsThere was a statistically significant difference between Graves' disease patients and the control group with respect to both the genotype distribution (P = 0.014) and allele frequency of rs744877 (P = 0.034). A significant association of CD160 rs744877 with AITD was observed before adjusted age and gender under a dominant model (OR = 0.79, 95%CI 0.66-0.95; P = 0.013) and an additive model (OR = 0.77, 95%CI 0.64-0.94, P = 0.008), and was also observed after adjusted age and gender under a dominant model (OR = 0.78, 95%CI 0.65-0.95; P = 0.011) and an additive model (OR = 0.76, 95%CI 0.63-0.93, P = 0.007). A significant association of rs744877 with Graves' disease was observed under an allele model (OR = 0.84, 95%CI 0.71-0.98, P = 0.027), a dominant model (OR = 0.74, 95%CI 0.60-0.91; P = 0.005), and an additive model (OR = 0.72, 95%CI 0.58-0.90, P = 0.004). Multivariate logistic regression analyses suggested that the association remained significant after adjustment for age and gender. However, rs744877 was not related to Hashimoto's thyroiditis. Furthermore, CD160 rs3766526 was not significantly related to either Graves' disease or Hashimoto's thyroiditis.ConclusionThis is the first identification of the association of CD160 rs744877 with Graves' disease. Our findings add new data to the genetic contribution to Graves' disease susceptibility and support the crucial role of the CD160/HVEM/LIGHT/BTLA pathway in the pathogenesis of Graves' disease.

Dataset Information

Network-Based Analysis Reveals Association of FOXE1 Gene Polymorphisms in Thyroid Cancer Patients; A Case-Control Study in Southeast of Iran.

Publications

Network-Based Analysis Reveals Association of FOXE1 Gene Polymorphisms in Thyroid Cancer Patients; A Case-Control Study in Southeast of Iran.

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