[COX6B2在胃癌中的高表达与长期预后不良相关，并通过抑制p53信号促进细胞增殖和细胞周期进程]
[High expression of COX6B2 in gastric cancer is associated with poor long-term prognosis and promotes cell proliferation and cell cycle progression by inhibiting p53 signaling].
作者信息
Shen M, Zhao N, Deng X, Deng M
机构信息
Department of Gastroenterology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
Anhui Provincial Biochemical Drug Research Engineering Center, Bengbu Medical College, Bengbu 233030, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Feb 20;44(2):289-297. doi: 10.12122/j.issn.1673-4254.2024.02.11.
OBJECTIVE
To investigate the effect of COX6B2 expression in gastric cancer tissues on the patients' long-term prognosis and its underlying mechanism.
METHODS
Based on the public databases and the medical records of patients, we analyzed the expression level of COX6B2 in gastric cancer and adjacent tissues and its influence on long-term prognosis of the patients. Enrichment analysis were used to predict the possible role of COX6B2 in gastric cancer. The effects of lentivirusmediated COX6B2 knockdown on biological behaviors of gastric cancer cells were examined using CCK-8 assay, flow cytometry, and Western blotting.
RESULTS
TCGA database and the results of immunohistochemistry, Western blotting and realtime PCR all demonstrated a significantly higher expression of COX6B2 in gastric cancer tissues ( < 0.05). Kaplan-Meier plotter database and Kaplan-Meier curves showed that the patients with high COX6B2 expression had significantly shorter postoperative survival ( < 0.05). A high expression of COX6B2 in gastric cancer tissues was closely correlated with clinicopathologic stage, CEA and CA19-9 ( < 0.05). A high expression of COX6B2, CEA level≥5 μg/L and CA19-9 level≥37 kU/L were independent risk factors affecting postoperative 5-year survival rate of gastric cancer patients ( < 0.05), and COX6B2 expression level had a predictive value for long-term prognosis of the patients ( < 0.05). GO and KEGG enrichment analyses showed that COX6B2 was mainly involved in the regulation of cell cycle. In the cell experiment, COX6B2 overexpression significantly promoted gastric cancer cell proliferation, increased the percentage of G1/S phase cells and inhibited the cellular expressions of p53 and p21 ( < 0.05).
CONCLUSION
s COX6B2 is highly expressed in gastric cancer and is closely correlated with a poor long-term prognosis of the patients possibly by promoting gastric cancer cell proliferation and regulating cell cycle.
目的
探讨胃癌组织中COX6B2表达对患者长期预后的影响及其潜在机制。
方法
基于公共数据库和患者病历，分析COX6B2在胃癌及癌旁组织中的表达水平及其对患者长期预后的影响。采用富集分析预测COX6B2在胃癌中的可能作用。利用CCK-8法、流式细胞术和蛋白质免疫印迹法检测慢病毒介导的COX6B2基因敲低对胃癌细胞生物学行为的影响。
结果
TCGA数据库以及免疫组织化学、蛋白质免疫印迹和实时荧光定量PCR结果均显示，COX6B2在胃癌组织中的表达显著升高（<0.05）。Kaplan-Meier plotter数据库和Kaplan-Meier曲线显示，COX6B2高表达患者术后生存期显著缩短（<0.05）。胃癌组织中COX6B2高表达与临床病理分期、癌胚抗原（CEA）和糖类抗原19-9（CA19-9）密切相关（<0.05）。COX6B2高表达、CEA水平≥5μg/L和CA19-9水平≥37 kU/L是影响胃癌患者术后5年生存率的独立危险因素（<0.05），且COX6B2表达水平对患者长期预后具有预测价值（<0.05）。基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析表明，COX6B2主要参与细胞周期调控。细胞实验中，COX6B2过表达显著促进胃癌细胞增殖，增加G1/S期细胞百分比，并抑制p53和p21的细胞表达（<0.05）。
结论
COX6B2在胃癌中高表达，可能通过促进胃癌细胞增殖和调控细胞周期与患者长期预后不良密切相关。
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