首页|CCAAT/增强子结合蛋白β作为预测胃癌预后潜在生物标志物的探究

CCAAT/增强子结合蛋白β作为预测胃癌预后潜在生物标志物的探究

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目的 本研究旨在探讨胃癌中CCAAT/增强子结合蛋白β(CEBPB)的潜在预后价值.方法 从肿瘤基因组图谱(TCGA)和基因表达数据库(GEO)数据集中下载CEBPB相关表达谱和相关临床数据,验证CEBPB在胃癌细胞系中的表达.采用基因集富集分析(GSEA)方法鉴定胃癌中CEBPB相关通路,并通过统计学分析评估胃癌中CEBPB表达与临床特征的相关性.通过细胞增殖实验(CCK-8)法、细胞划痕实验和菌落形成实验探讨CEBPB在胃癌中的具体功能.结果 CEBPB在胃癌组织中表达显著高于非肿瘤组织(2 870.0±4485.0比908.1±957.6,t=6.264,P<0.05),并且CEBPB在胃癌细胞系AGS,MKN-45,HGC-27中表达高于GES-1.此外,CEBPB高表达患者组平均总生存期(OS)显著低于低表达患者组;CEBPB高表达患者组平均首次进展期(FP)低于低表达组.GSEA发现与CEBPB与多种肿瘤进展相关信号通路及生物学过程有关(PID SMAD23NUCLEAR通路、凋亡负调控信号通路、VEGFA-VEGFR2信号通路、IL-4信号通路、RNA生物合成过程等).CEBPB 蛋白网络分析提示其与蛋白 ATF4、CEBPA、CEBPD、DDIT3、EP300、HDAC1、MYB、PPARG、PRDM16、STAT3存在互作联系.CCK-8显示CEBPB敲减组细胞增殖低于对照组(0.51± 0.05 比 0.68±0.17、0.32±0.05 比 0.68±0.17,t=2.950、6.280,P<0.05).克隆实验示 CEBPB 敲减组克隆形成数少于对照组(148.0±60.1 比 681.0±156.5、491.0±175.0 比 681.0±156.5,t=1.400、5.510,P<0.05);划痕实验示CEBPB敲减组细胞迁徙率比值显著高于对照组(0.86±0.07比 0.71±0.04、0.87±0.03 比 0.71±0.04,t=5.110、8.920,P<0.05).结论 CEBPB 在胃癌中具有致瘤作用,可能是胃癌的临床预后的重要因素.
CCAAT/enhancer binding protein p as a potential biomarker for predicting the prognosis of gastric cancer
Objective To explore the potential prognostic value of CCAAT/enhancer-binding pro-tein beta(CEBPB)in gastric cancer.Methods CEBPB-related expression profiles and relevant clinical data were downloaded from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)data-sets to validate the expression of CEBPB in gastric cancer cell lines.Gene Set Enrichment Analysis(GSEA)was employed to identify CEBPB-related pathways in gastric cancer.The correlation between CEBPB expression and clinical features in gastric cancer was assessed through statistical analysis.The spe-cific functions of CEBPB in gastric cancer were explored through cell proliferation experiments(cell count-ing kit-8,CCK-8),cell scratch assays,and colony formation assays.Statistical analyses were performed u-sing SPSS 26.0 and GraphPad Prism 7.Results CEBPB expression in gastric cancer tissues was signifi-cantly higher than in non-tumor tissues(2 870.0±4 485.0 vs.908.1±957.6,t=6.264,P<0.05),and CEBPB expression in gastric cancer cell lines(AGS,MKN-45,HGC-27)was higher than in GES-1 cells.Furthermore,patients with high CEBPB expression had significantly lower average overall survival(OS)and first progression(FP)than low-expression patients.GSEA revealed associations between CEBPB and various signaling pathways and biological processes related to tumor progression(PID SMAD23NUCLEAR pathway,apoptosis negative regulation signaling pathway,VEGFA-VEGFR2 signaling path-way,IL-4 signaling pathway,RNA biosynthetic process,etc.).Protein network analysis of CEBPB sug-gested interactions with ATF4,CEBPA,CEBPD,DDIT3,EP300,HDAC1,MYB,PPARG,PRDM16,and STAT3.CCK-8 assays showed that cell proliferation in the CEBPB knockdown group was lower than in the control group(0.51±0.05 vs.0.68±0.17,0.32±0.05 vs.0.68±0.17,t=2.950,6.280,P<0.05).Cloning experiments demonstrated that the CEBPB knockdown group had fewer colonies than the control group(148.0±60.1 vs.681.0±156.5,491.0±175.0 vs.681.0±156.5,t=1.400,5.510,P<0.05),and scratch assays showed that the migration rate of the CEBPB knockdown group was signifi-cantly higher than the control group(0.86±0.07 vs.0.71±0.04,0.87±0.03 vs.0.71±0.04,t=5.110,8.920,P<0.05).Conclusion The study revealed that CEBPB plays an oncogenic role in gas-tric carcinoma and may serve as a clinical prognostic factor for gastric carcinoma.

Gastric cancerPrognosis

郑扬、张鹏善、米兰、林欢、黄陈

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蚌埠医学院研究生院,安徽 233030

上海交通大学医学院附属第一人民医院胃肠外科,上海 200080

胃癌 预后

国家自然科学基金项目国家自然科学基金项目国家自然科学基金项目上海市抗癌协会EYAS项目

82072662822037518200102297SACACY21C08

2024

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子:0.759
ISSN:1001-9030
年,卷(期):2024.41(2)
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