Integrative Bioinformatics Analysis of iNOS/NOS2 in gastric and colorectal cancer

Abstract

Objective The aim of the present work was to investigate the expression of nitric oxide synthase 2 (iNOS/ NOS2) in colorectal and gastric cancers and evaluate its association with patient's prognosis by integrated bioinformatics analysis. Methods The data for present study was obtained from the TCGA, GTEx, and STRING database. iNOS/NOS2 mRNA expression in normal tissue and colorectal, and gastric cancer tissuea were investigated through the GTEx and TCGA database. iNOS/NOS2 gene mutations and frequency were analyzed in the TCGA database using the cBioPortal online data analysis tool. The protein-protein interaction (PPI) network of iNOS/NOS2 was constructed by STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of iNOS/NOS2 and relevant proteins involved in the PPI network were enriched and demonstrated by the bubble plot. Comparison of the overall survival(OS) and disease free survival(DFS) between samples expressing high and low levels of iNOS/NOS2 was analysis based on the TCGA databases through the GEPIA online data analysis tool. Results For colon adenocarcinoma (COAD) and rectal adenocarcinoma(READ) iNOS/NOS2 mRNA expression levels in tumor tissue were significant higher than those of corresponding normal colorectal tissue (p<0.05). iNOS/NOS2 mutations were identified in both colorectal cancer and gastric cancer. Missense substitutions and synonymous substitution were the top two mutation types for colorectal and gastric cancer. The top positive and negative co-expressed genes correlated with iNOS/ NOS2 were TRIM40 (rpearson=0.56, p<0.05) and GDPD5 (rpearson=-0.41, p<0.05) in colorectal cancer respectively andCASP5 (rpearson=0.63,p<0.05) and PIAS3 (rpearson=-0.43,p<0.05) in gastric cancer. Twenty one proteins were included in the PPI network with 51 nodes and 345 edges which indicated the PPI enrichment wassignificant (p=1.0e-16). The KEGG of the included genes were mainly enriched in metabolic pathway and Jak-STAT signaling pathway. There was a significant difference indisease free survival (DFS) between samples expressing high and low iNOS/NOS2 (HR=0.37, p=0.044) in rectal cancer. The difference was not statistical between iNOS/NOS2 high and low expressing groups for overall survival(OS) or DFS in the colon cancer or gastric cancer(p>0.05). Conclusions iNOS/NOS2 mRNA isup-regulated in tumor tissue compared to corresponding normal tissue in colorectal and gastric cancer which implement it in the development of colorectal and gastric cancers.