Induction of mTOR signaling pathway in the progression of papillary thyroid cancer

Abstract

Papillary thyroid carcinoma (PTC) is the most frequent (more than 85%) malignancy among the four pathological types of thyroid cancer. Since enhancements of survival and recurrence rates of the disease as well as early diagnosis are essential, the genome-wide investigation for identifying robust biomarkers for PTC patients is necessary.In the current research, two independent gene expression omnibus (GEO) datasets resulted from systematically searching the NCBI-GEO database and applying the inclusion and exclusion criteria for PTC patients. Then, the identification of significant biomarkers through a meta-analysis approach used the associated genes of the mTOR signaling pathway. The survival analysis of the determined genes included overall survival (OS) and recurrence-free survival (RFS) rates based on The Cancer Genome Atlas dataset. Furthermore, the analysis and virtual screening process were carried out for finding potential drugs and drug-like ligands.The analysis outcomes reveal three statistically significant downregulated biomarkers IRS1, DEPTOR, and PRKCA between PTC and healthy tissues with experimental literature confirmation. Moreover, the survival analysis shows that DEPTOR and PRKCA have vital roles in RFS (p-value = .012) and OS (p-value = .045) rates, respectively. However, IRS1 does not present significant p-value in terms of RFS and OS rates. The GDIdbi webserver found twenty, three, and four potential drugs for PRKCA, DEPTOR, and IRS1. And two molecules had structural interactions with IRS1 with four hydrogen bond acceptors through the virtual screening procedure.Consequently, the critical role of genome-wide association studies (GWAS) should not be of ignorance in diagnosing PTC patients. Furthermore, the outcomes of such GWAS investigations need to be carefully involved in the future development of new therapeutic agents.