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

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.