PCID2在胃癌中高表达，并通过调节癌细胞周期和增殖影响预后。
[PCID2 is highly expressed in gastric cancer and affects the prognosis by regulating cancer cell cycle and proliferation].
作者信息
Zhang N, Zhang Z, Zhang Y, Song X, Zhang X, Li J, Zuo L, Hu J
机构信息
Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, China.
Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Feb 20;44(2):324-332. doi: 10.12122/j.issn.1673-4254.2024.02.15.
OBJECTIVE
To investigate the expression of PCI Domain Containing 2 (PCID2) in gastric cancer, its effect on gastric cancer cell cycle and proliferation and the possible molecular mechanisms.
METHODS
We examined PCID2 expression levels in gastric cancer and adjacent tissues from 100 patients undergoing radical gastrectomy in our hospital between January, 2012 and December, 2016, and analyzed the correlation of PCID2 expression level with cancer progression and postoperative 5-year survival rate of the patients. GO enrichment analysis was performed to identify the possible pathways that mediated the effect of PCID2 in gastric cancer progression. The effects of lentivirus-mediated PCID2 knockdown and overexpression on cell proliferation and cell cycle were analyzed in gastric cancer MGC-803 cells and in nude mice.
RESULTS
PCID2 was highly expressed in gastric cancer tissues and positively correlated with peripheral blood levels of CA19-9 and CEA ( < 0.01). In gastric cancer patients, a high PCID2 expression was associated with a significantly lowered postoperative 5-year survival rate ( < 0.001) as an independent risk factor for postoperative survival (HR: 2.987, 95% : 1.616-5.519). The sensitivity, specificity, and area under the curve of PCID2 for predicting postoperative 5-year survival were 76.74%, 75.44%, and 0.755 ( < 0.001), respectively. GO enrichment analysis suggested that PCID2 was associated with gastric cancer cell cycle progression. PCID2 overexpression in MGC-803 cells significantly promoted cell proliferation, G1/S phase transition, expressions of cyclin D1 and CDK6, and the growth of transplanted xenograft in nude mice ( < 0.05). The expressions of p27 and p16 were significantly lowered in gastric cancer tissues, and their expression levels were negatively regulated by PCID2 expression in MGC-803 cells ( < 0.05).
CONCLUSION
PCID2 is highly expressed in gastric cancer tissues in close correlation with poor prognosis of the patients. High PCID2 expression promotes gastric cancer proliferation and cell cycle progression by inhibiting the expression of p27 and p16.
目的
探讨含PCI结构域蛋白2（PCID2）在胃癌中的表达情况、其对胃癌细胞周期及增殖的影响以及可能的分子机制。
方法
检测2012年1月至2016年12月在我院接受根治性胃切除术的100例患者的胃癌组织及癌旁组织中PCID2的表达水平，并分析PCID2表达水平与肿瘤进展及患者术后5年生存率的相关性。进行基因本体（GO）富集分析以确定介导PCID2在胃癌进展中作用的可能途径。分析慢病毒介导的PCID2基因敲低和过表达对胃癌MGC-803细胞及裸鼠细胞增殖和细胞周期的影响。
结果
PCID2在胃癌组织中高表达，且与外周血CA19-9和CEA水平呈正相关（P<0.01）。在胃癌患者中，PCID2高表达与术后5年生存率显著降低相关（P<0.001），是术后生存的独立危险因素（风险比：2.987，95%置信区间：1.616-5.519）。PCID2预测术后5年生存的敏感性、特异性及曲线下面积分别为76.74%、75.44%和0.755（P<0.001）。GO富集分析表明PCID2与胃癌细胞周期进展相关。MGC-803细胞中PCID2过表达显著促进细胞增殖、G1/S期转换、细胞周期蛋白D1和细胞周期蛋白依赖性激酶6的表达以及裸鼠移植瘤生长（P<0.05）。胃癌组织中p27和p16表达显著降低，MGC-803细胞中其表达水平受PCID2表达的负调控（P<0.05）。
结论
PCID2在胃癌组织中高表达，与患者预后不良密切相关。PCID2高表达通过抑制p27和p16的表达促进胃癌增殖和细胞周期进展。
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