摘要
背景与目的:Polo样蛋白激酶4(Polo-like kinases 4,PLK4)主要参与调控中心体的复制进程,过表达PLK4能够诱导肿瘤细胞中心体扩大、染色体不稳定及肿瘤侵袭性增强。该研究旨在探讨PLK4在人结直肠癌(colorectal cancer,CRC)中的表达及临床意义。方法:收集19例CRC组织及对应癌旁组织的新鲜标本,129例CRC组织及癌旁组织的石蜡标本。应用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerasechainreaction,RTFQ-PCR)检测19例CRC组织及对应癌旁组织中PLK4mRNA的表达;采用免疫组织化学法检测129例CRC患者手术切除石蜡标本的PLK4蛋白的水平,分析PLK4表达与CRC临床病理指标之间的相关性及与预后的相关性。结果:RTFQ-PCR显示,PLK4 mRNA表达在CRC组织中明显高于癌旁组织(P<0.01),免疫组织化学结果显示,PLK4蛋白阳性信号定位于细胞质及部分细胞核。PLK4蛋白在129例CRC组织中低表达62例,高表达67例,PLK4蛋白在CRC组织中的表达显著高于癌旁组织(P<0.01),PLK4蛋白水平与CRC分化程度(P=0.001 1)、N分期(P<0.000 1)、M分期(P=0.035 8)和TNM分期(P<0.000 1)呈正相关。Kaplan-Meier生存曲线显示,PLK4低表达组中位生存时间为27个月,高表达组中位生存时间为12个月,组间总生存率(overall survival,OS)差异有统计学意义,PLK4高表达组OS明显低于PLK4低表达组(P<0.000 1)。多因素COX比例风险模型分析显示,PLK4高表达不是CRC的独立预后因素(P=0.176)。结论:PLK4在CRC组织中高表达,并且与CRC组织分化差、淋巴结转移、远处转移及TNM分期相关;PLK4高表达提示CRC预后差,但不是独立预后因素。
Background and purpose： Polo-like kinase 4（PLK4） is mainly involved in regulation of the replication process of centrosome. Overexpression of PLK4 can induce the enlargement of the centrosome, cause instability of the chromosomes, and enhance tumor invasiveness. The purpose of this research was to investigate the expression of PLK4 in human colorectal cancer（CRC）, and evaluate its clinicopathological significance. Methods： Fresh tissues of 19 cases of CRC and adjacent normal tissues were collected, and paraffin specimens of 129 cases of CRC tissues and adjacent tissues were collected. PLK4 mRNA expression was measured from 19 cases of CRC and corresponding normal tissues by real-time fluorescent quantitative polymerase chain reaction（RTFQ-PCR）. Immunohistochemical staining was performed to detect the PLK4 expression in 129 cases of CRC and corresponding normal tissues. The association of the PLK4 expression with clinicopathological parameters and prognostic significance was evaluated. Results： The level of PLK4 mRNA expression in CRC tissues was significant higher than in the corresponding normal tissues（P〈0.01）. Immunohistochemical staining showed PLK4 protein was localized in cytoplasm and part of nucleus in CRC cells. In 129 cases of CRC, low expression of PLK4 protein was found in 62 cases whereas PLK4 protein was highly expressed in 67 cases. PLK4 protein expression in CRC was significantly higher than that in adjacent tissues（P〈0.01）. There was a correlation of PLK4 expression with higher histological grading（P=0.001 1）, higher incidence of lymph node metastasis（P〈0.000 1）, distant metastasis（P=0.035 8） and TNM staging（P〈0.000 1）. Kaplan-Meier survival curves showed that the median survival time was 27 months in PLK4 protein low expression group, and 12 months in PLK4 protein high expression group. Log-rank test results showed that high PLK4 expression was found to be a detrimental prognostic factor measured by overall survival（OS）（P〈0.000 1）. Mult
作者
蒋浩海
肖锋
顾春燕
周林森
高一飞
穆向明
JIANG Haohai;XIAO Feng;GU Chunyan;ZHOU Linsen;GAO Yifei;MU Xiangming(Department of General Surgery,Yancheng First People＇s Hospital,Yancheng 224001,Jiangsu Province,China;Department of Pathology,Affiliated Nantong Third Hospital of Nantong University,Nantong 226006,Jiangsu Province,China)
出处
《中国癌症杂志》
CAS
CSCD
北大核心
2018年第9期686-691,共6页
China Oncology
基金
南通市市级科技计划项目(MS22015087
GJZ16007)
