ROLE OF TUMOR NECROSIS FACTOR-?ETA (TNF-?) IN GASTRIC CANCER: SINGLE NUCLEOTIDE POLYMORPHISMS ANALYSIS-AN IN-SILICO STUDY

Abstract

Tumor necrosis factor-beta is also called lymphotoxin-alpha. The objective of this study was to identify non-synonymous SNPs of TNF-beta and their association with gastric cancer using computational analysis. For this purpose, different online tools like SIFT, Polyphen, Polyphen-2, fuNTRp, SNAP2 (to identify pathogenic SNPs), SNP&GO, PhD-SNP, PredictSNP, MAPP, SNAP, MetaSNP, PANTHER (disease associated SNPs), Mu-Pro, I-Mutant, and CONSURF (to check protein stability) were used. Post-translational modifications (PTMs) were detected by Musitedeep, Protein secondary structure by SOPMA, and Protein to protein interaction by STRING. Three SNPs having rsIDs (rs1325992410, rs1290487566, and rs769344065) showing mutations on Y110C, G117E, and G170R, respectively found to be completely deleterious. The PTMs found were phosphorylation at amino acid number 2 and 128; palmitoylation at number 13; pyrrolidone carboxylic acid at number 33 and glycosylation at number 41 and 46. The protein secondary structure consisted of alpha helix (18.54%), extended strand (29.27%), beta turn as 6.83% and random coil (45.37%). Protein-protein interaction analyses revealed that it has strong interaction with Mitogen Activated Protein (MAP) kinase (MAP3K14). Based on these results, it is concluded that these three SNPs found in TNF-B are involved in gastric cancer.