子宫内膜癌组织CCNA2、CDCA8表达与增殖侵袭基因、临床病理参数及预后的关系研究

Relationships of CCNA2 and CDCA8 expressions in endometrial carcinoma tissues with proliferation genes and invasion genes, clinicopathological parameters and prognosis of the disease

摘要

目的 探讨子宫内膜癌(EC)组织中细胞周期蛋白A2(CCNA2)、细胞分裂周期相关基因8(CDCA8)表达情况与增殖侵袭基因表达、临床病理参数和预后的关系。方法 选择2016年1月至2020年2月在河北北方学院附属第一医院进行手术治疗的203例EC患者为研究对象。采用实时荧光定量聚合酶链式反应(RT-qPCR)检测EC组织及癌旁组织CCNA2、CDCA8表达及增殖基因[细胞周期蛋白依赖激酶6(CDK6)、增殖细胞核抗原(PCNA)、细胞周期素D1(CCND1)、核苷酸还原酶M2(RRM2)]、侵袭基因[高迁移率族蛋白B1(HMGB1)、Dickkopf相关蛋白1(DKK1)、转移关联蛋白1(MTA1)]的表达情况及相关性,并分析EC组织中CCNA2、CDCA8表达与患者临床病理参数的关系;采用Kaplan-Meier生存曲线分析CCNA2、CDCA8高表达与低表达对EC患者预后的影响。结果 EC癌组织中CCNA2、CDCA8、CDK6、PCNA、CCND1、RRM2、HMGB1、MTA1的mRNA相对表达量高于癌旁组织,差异有统计学意义(t值介于11.986~30.927之间,P<0.05);EC癌组织中DKK1的mRNA相对表达量低于癌旁组织,差异有统计学意义(t=17.033,P<0.05);EC组织中CCNA2、CDCA8的mRNA相对表达量与CDK6、PCNA、CCND1、RRM2、HMGB1、MTA1的mRNA相对表达量呈正相关性(r值介于0.538~0.665之间,P<0.05),与DKK1的mRNA相对表达量呈负相关性(r值分别为-0.593、-0.606,P<0.05);EC癌组织中CCNA2、CDCA8的mRNA相对表达量在国际妇产科联盟(FIGO)分期Ⅲ期组、低分化组、肌层浸润深度≥1/2组、淋巴结转移组中较高,差异有统计学意义(t值介于6.948~13.894之间,P<0.05);高CCNA2组3年总生存率为72.34%,低于低CCNA2组的91.43%,差异有统计学意义(χ²=12.405,P<0.001);高CDCA8组3年总生存率为71.43%,低于低CDCA8组的93.07%,差异有统计学意义(χ²=15.990,P<0.001)。结论 子宫内膜癌组织中CCNA2、CDCA8呈高表达状态,其表达水平与增殖侵袭基因、临床病理参数有关,其表达水平升高有可能导致子宫内膜癌患者预后不良。

Abstract

Objective To investigate relationships of expressions of cyclin A2 (CCNA2) and cell division cycle-related gene 8 (CDCA8) in endometrial carcinoma (EC) tissues with expressions of proliferation genes and invasion genes, clinicopathological parameters and prognosis of the disease. Methods 203 EC patients who underwent surgical treatment in The First Affiliated Hospital of Hebei North University from January 2016 to February 2020 were selected as study subjects. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was employed to detect expressions of CCNA2, CDCA8 and proliferation genes [cyclin-dependent kinase 6 (CDK6), proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1), ribonucleotide reductase M2 (RRM2)], invasion genes [high mobility group protein B1 (HMGB1), Dickkopf-related protein 1 (DKK1), metastasis-associated protein 1 (MTA1)] in EC tissues and adjacent tissues of EC patients. Pearson correlation analysis was used to analyzed correlations of expressions of CCNA2 and CDCA8 with expressions of CDK6, PCNA, CCND1, RRM2, HMGB1, DKK1 and MTA, and relationships of expressions of CCNA2 and CDCA8 in EC tissues with clinicopathological parameters of the patients. Kaplan-Meier survival curve was used to analyze effects of high expressions and low expressions of CCNA2 and CDCA8 on prognosis (overall 3-year survive rate) of EC patients. Results The relative mRNA expression levels of CCNA2, CDCA8, CDK6, PCNA, CCND1, RRM2, HMGB1 and MTA1 in EC tissues were higher than those in the adjacent tissues, the differences were statistically significant (t=11.986-30.927, all P<0.05), while the relative expression of DKK1 mRNA in EC tissues was lower than that in the adjacent tissues, and the difference was statistically significant (t=17.033, P<0.05). The relative mRNA expressions of CCNA2 and CDCA8 in EC tissues were positively correlated with the relative mRNA expressions of CDK6, PCNA, CCND1, RRM2, HMGB1 and MTA1 (r=0.538-0.665, all P<0.05), while they were negatively correlated with the relative mRNA expression of DKK1 (r=-0.593 and -0.606 respectively, both P<0.05). The relative expression levels of CCNA2 mRNA and CDCA8 mRNA in EC tissues were related to clinicopathological parameters such as International Federation of Gynecology and Obstetrics (FIGO) staging, degree of differentiation, depth of myometrial invasion and lymph node metastasis: in detail, the relative expression levels of CCNA2 mRNA and CDCA8 mRNA in such EC tissues groups as FIGO stage III subgroup, low differentiation group, depth of myometrial invasion ≥1/2 group and lymph node metastasis group were higher, and the differences were statistically significant (t=6.948-13.894, all P<0.05). The overall 3-year survival rate of EC patients in high CCNA2 expression group was 72.34%, which was lower than 91.43% in low CCNA2 expression group, the difference was statistically significant (χ²=12.405, P<0.001). The overall 3-year survival rate of EC patients in high CDCA8 expression group was 71.43%, which was lower than 93.07% in low CDCA8 expression group, the difference was statistically significant (χ²=15.990, P<0.001). Conclusion CCNA2 and CDCA8 are highly expressed in EC tissues, and their expression levels are related to proliferation genes and invasion genes, and clinicopathological parameters of the patients. Elevated expression levels of CCNA2 and CDCA8 can lead to poor prognosis of EC patients.

关键词

子宫内膜癌 / 细胞周期蛋白A2 / 细胞分裂周期相关基因8 / 增殖基因 / 侵袭基因 / 临床病理参数 / 预后

Key words

endometrial carcinoma / cyclin A2 / cell division cycle-related gene 8 / proliferation gene / invasion gene / clinicopathological parameter / prognosis

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基金资助

河北省2024年度医学科学研究课题计划(20240274)