Comprehensive analysis of gene mutation and expression profiles in neuroendocrine carcinomas of the stomach

Abstract

The gene mutation and expression profiles of gastric neuroendocrine carcinoma (NEC) have not been comprehensively determined. Here, we examined the gene mutation and expression profiles of NEC using whole exome sequencing (WES) and microarray analysis. Six patients with gastric NEC and 13 with gastric adenocarcinoma (GAD) were included in this study. Single nucleotide variants were compared and multivariate statistical investigation with orthogonal partial least squares discriminant analysis (OPLS-DA) was performed to compare the difference in expression profiles between NEC and GAD. NEC showed a significantly higher mutation rate than GAD and the percentage difference in the mutation pattern of NEC compared with GAD was 92.8%. OPLSDA clearly discriminated between NEC and GAD. We identified 35 genes, including CPLX2 (Complexin 2), which were expressed more strongly in NEC than in GAD, of which 14 were neural- related. Immunohistochemical analysis showed the strong expression of CPLX2 in all NECs, versus expression in only 2 of 13 GADs. Gastric NEC had a specific mutation pattern with a significantly higher gene mutation rate than GAD, and completely differed from GAD on the basis of gene expression profile. CPLX2 might be a potential novel biomarker for the diagnosis of NEC.