Bioinformatics Analysis Identifies NDRG1 Gene Variants that may be Clinically Relevant
Author(s): Borré GB, Pimenta AT, Chmieleski GS, Moyses GR, Souza SCB, Rabi LT, Peres KC, Teixeira ES, Bufalo NE, Ward LS.
Background: The search of single nucleotide variants that might have the capacity to alter genetic information and influence in regular cellular pathways, enhancing expansion, mitosis and evasion capacity to neoplasm cells, is central in understanding the molecular nature of distinct cellular growth abnormalities and is critical because it might expose new possibilities for therapeutic targets. The expression of NDRG1 protein, encoded by NDRG1 gene, has already been correlated with tumor progression and evasion, but information on different types of neoplasm is still contentious.
Objective: To explore probable correlations of susceptibleness, progression and clinical characteristics between NDRG1 gene polymorphisms (SNPs) and patients that developed thyroid tumors.
Methods: SNPs were obtained from the NCBI dbSNP. The encoded protein primary sequences were got from the UniProt database. We employed the three FASTA primary sequences to analyze the amino acid changes. The bioinformatics tools used were: PredictSNP1.0 (which encompasses: PANTHER, SNAP, PolyPhen-1, PhD-SNP, nsSNPAnalyze, SIFT, PredictSNP, PolyPhen-2, MAPP,); I-Mutant2.0; MUpro; PROVEAN; Haploview and SNPs3D).
Results: The NCB database reports 319 missense SNPs in the NDRG1 gene. The SIFT tool predicted that 51 nsSNPs of 109 (which means 46.78%) were deleterious; the SNAP tool predicted nearly 30%; PolyPhen-2, 53 (48.62%); 52 (47.70%) derived from PhD-SNP; PolyPhen-1 indicated 38 nsSNPs (approximately 35%); and MAPP showed 47 (which is 43%). Finally, the PredictSNP toll contemplated 13 (approximately 12%) nsSNPs deleterious by all integrated tools, including rs201348291 and rs15132213, whose scores were the most significant, thus indicating a higher possibility that these SNPs are correlated and influence the pathophysiology of thyroid neoplasm.
Conclusions: We demonstrated that NDRG1 rs201348291 and rs151322132 may be involved in thyroid cancer emergence and deserve further validation and evaluation of their clinical applicability in determining the risk of thyroid nodules malignancy and thyroid cancer prognostic.