The potential clinical implication of CEACAM6 overexpression in gastric cancer

doi:10.3969/j.issn.1009-976X.2022.03.001

Abstract

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

摘要： 目的 CEACAM6可促进胃癌进展,但机制尚不明确,本研究旨在评价CEACAM6表达意义并初步探究其潜在分子通路。方法下载胃癌芯片和高通量测序数据,提取并计算CEACAM6 mRNA表达值标准化平均差（SMD）,结合人类蛋白质图谱免疫组化染色结果,从基因和蛋白层面验证胃癌CEACAM6表达水平。用汇总受试者工作特征曲线法评估CEACAM6表达对甄别胃癌的潜在价值。用基因差异表达分析鉴定胃癌中异常表达的CEACAM6共表达基因,并注释功能;基于富集通路构建蛋白质交互网络,寻找枢纽基因。最后比较胃癌患者CEACAM6和枢纽基因突变。结果本研究共纳入胃癌数据集24个,整合了来自世界各地的1531例胃癌组织样本及686例正常胃组织样本。CEACAM6在胃癌组织中被明显上调[SMD=0.72（0.47~0.97）],对胃癌有中等区分能力[AUC=0.82（0.78~0.85）],但其高表达水平在不同性别、年龄及肿瘤分期的胃癌患者中无显著差异。CEACAM6共表达基因显著富集于“中间丝细胞骨架”“金属离子跨膜转运活性”与“胰腺分泌”中。SPRR3可能为CEACAM6共表达枢纽基因,与CEACAM6有明显突变互斥现象。结论 CEACAM6在胃癌中表达上调,可作为胃癌筛查和治疗潜在靶点。

关键词: 胃癌, CEACAM6, 共表达网络, 分子机制

CLC Number:

R735.2

LI Jian-di, YANG Li-hua, HE Rong-quan, LAI Qian-yao, CHEN Si-zhi, CHEN Chuan-liang, LI Jian-jun, CHEN Zu-xuan. The potential clinical implication of CEACAM6 overexpression in gastric cancer[J]. Lingnan Modern Clinics In Surgery, 2022, 22(03): 213-222.

李建棣, 杨丽桦, 何融泉, 赖倩瑶, 陈思智, 陈传良, 李建军, 陈祖轩. CEACAM6高表达在胃癌患者中的潜在临床价值[J]. 岭南现代临床外科, 2022, 22(03): 213-222.

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