title: 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.
authors.affiliation: Division of Gastric Surgery, Shizuoka Cancer Center.
authors.forename: Rie
authors.initials: R
authors.lastname: Makuuchi
authors.forename: Masanori
authors.initials: M
authors.lastname: Terashima
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kusuhara
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Masakuni
authors.initials: M
authors.lastname: Serizawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hatakeyama
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Kenichi
authors.initials: K
authors.lastname: Urakami
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000368:Aged; D018278:Carcinoma, Neuroendocrine / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D016002:Discriminant Analysis; D005260:Female; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D059645:Mutation Rate; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics*; D059467:Transcriptome
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; C095993:complexin II