关键词: 胃癌, CEACAM6, 共表达网络, 分子机制

Abstract: Objective CEACAM6 can promote the progression of gastric cancer （GC）, but the mechanism is still unclear. This study aimed to evaluate the expression of CEACAM6 and explore its potential molecular pathways. Methods The GC microarray and high-throughput sequencing data were downloaded, and the standardized mean difference （SMD） of CEACAM6 mRNA expression values was calculated. Combined with the results of immunohistochemical staining from The Human Protein Atlas, the expression levels of CEACAM6 in GC were verified from the gene and protein levels. The potential value of CEACAM6 expression in discriminating GC was assessed by the summary receiver operating characteristic curve method. Differential gene expression analysis was used to identify abnormally expressed CEACAM6 co-expressed genes in GC, and their molecular functions were annotated. Based on enrichment pathways, protein-protein interaction network was constructed to find hub genes. Finally, the somatic mutations of CEACAM6 and hub genes were compared in GC patients. Results A total of 24 GC datasets were included in this study, integrating 1531 GC tissue samples and 686 normal gastric tissue samples from around the world. CEACAM6 was significantly up-regulated in GC tissues [SMD=0.72 （0.47~0.97）], and had moderate discriminative ability for GC [AUC=0.82 （0.78~0.85）], but its high expression level in gender, age and tumor stage were insignificant. CEACAM6 co-expressed genes were significantly enriched in intermediate filament cytoskeleton, metal ion transmembrane transport activity and pancreatic secretion. SPRR3 may be a co-expression hub gene of CEACAM6, and its mutations exhibited mutual exclusion with CEACAM6. Conclusion CEACAM6 is up-regulated in GC and may be used as a potential target for GC screening and treatment.

Key words: gastric cancer, CEACAM6, co-expression network, molecular mechanism