Zhang Z, Lu H, Chen X, Wang L, Wang Z, Wang Y, Ge S, Zuo L
Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China.
Graduate School, Bengbu Medical University, Bengbu 233030, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Nov 20;44(11):2137-2145. doi: 10.12122/j.issn.1673-4254.2024.11.10.
To investigate the correlation of CEP192 expression with prognosis of gastric cancer and biological behaviors of gastric cancer cells.
Public databases and clinical tissue samples were used to examine CEP192 expression level in gastric cancer. Kaplan-Meier survival curves, univariate and multivariate Cox regression analyses, ROC curves and bioinformatics analyses were used to explore the risk factors affecting the 5-year postoperative survival, the correlation of CEP192 expression level with the patients' survival, and its biological role in gastric cancer development. In gastric cancer MGC-803 cells with lentivirus-mediated CEP192 interference or overexpression, cell proliferation and expressions of PLK1, CDK1 and Cyclin B1 were examined with CCK-8 assay and Western blotting. The effects of CEP192 knockdown or overexpression on tumorigenesis of MGC-803 cells was observed in nude mice, and the expressions of PLK1, CDK1 and Cyclin B1 in the xenografts were detected.
CEP192 was highly expressed in gastric cancer and associated with poor prognosis of the patients ( < 0.05). High expression of CEP192, CEA ≥5 ng/mL, CA199 ≥37 IU/mL, T3-4 stage, and N2-3 stage were independent risk factors affecting the patients' 5-year postoperative survival ( < 0.05). Bioinformatics analyses suggested that CEP192 was involved in several vital biological processes and positively regulated cell cycle progression. In MGC-803 cells, CEP192 knockdown significantly inhibited cell proliferation and lowered the expression levels of PLK1, CDK1, and Cyclin B1, while its overexpression produced the opposite effects. In the nude mouse models, CEP192 knockdown resulted in lowered tumorigenic potential of MGC-803 cells and decreased protein levels of PLK1, CDK1, and Cyclin B1 in the xenografts, while CEP192 overexpression in MGC-803 cells caused the opposite changes.
CEP192 overexpression is correlated with unfavorable outcomes of gastric cancer patients and promotes gastric cell proliferation by regulating the key proteins during G2/M phase transition.
探讨CEP192表达与胃癌预后及胃癌细胞生物学行为的相关性。
利用公共数据库和临床组织样本检测胃癌中CEP192表达水平。采用Kaplan-Meier生存曲线、单因素和多因素Cox回归分析、ROC曲线及生物信息学分析，探讨影响术后5年生存的危险因素、CEP192表达水平与患者生存的相关性及其在胃癌发生发展中的生物学作用。在慢病毒介导的CEP192干扰或过表达的胃癌MGC-803细胞中，采用CCK-8法和蛋白质印迹法检测细胞增殖及PLK1、CDK1和Cyclin B1的表达。在裸鼠中观察CEP192敲低或过表达对MGC-803细胞致瘤性的影响，并检测异种移植瘤中PLK1、CDK1和Cyclin B1的表达。
CEP192在胃癌中高表达，与患者预后不良相关（<0.05）。CEP192高表达、CEA≥5 ng/mL、CA199≥37 IU/mL、T3-4期和N2-3期是影响患者术后5年生存的独立危险因素（<0.05）。生物信息学分析表明，CEP192参与多个重要生物学过程，正向调控细胞周期进程。在MGC-803细胞中，CEP192敲低显著抑制细胞增殖，降低PLK1、CDK1和Cyclin B1的表达水平，而过表达则产生相反作用。在裸鼠模型中，CEP192敲低导致MGC-803细胞致瘤潜能降低，异种移植瘤中PLK1、CDK1和Cyclin B1蛋白水平降低，而MGC-803细胞中CEP192过表达则引起相反变化。
CEP192过表达与胃癌患者不良预后相关，通过调控G2/M期转换过程中的关键蛋白促进胃细胞增殖。
