宫颈癌PI3K/Akt/mTOR信号通路相关蛋白的表达及与临床病理特征和预后的关系

Expression of protein associated with PI3K/Akt/mTOR signaling pathway in cervical cancer and its relationship with clinicopathological characteristics and prognosis

目的:探究宫颈癌患者病理组织中磷脂酰肌醇-3-激酶/蛋白激酶B/雷帕霉素靶体蛋白(phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin,PI3K/Akt/mTOR)信号通路相关蛋白的表达,及其与临床病理参数和预后的关系。方法:收集2016年1月至2018年1月于遵义市第一人民医院就诊的61例宫颈癌患者活检及手术宫颈癌标本。采用免疫组织化学法检测PI3K、p-Akt、p-mTOR的表达。宫颈癌患者PI3K、Akt、mTOR表达与临床病理特征的关系采用多因素logistic回归模型分析,与预后的关系采用Kaplan-Meier生存曲线分析。结果:宫颈癌组织PI3K、p-Akt、p-mTOR阳性率均高于癌旁组织(χ^(2)=64.050,P=0.000;χ^(2)=58.607,P=0.000;χ^(2)=56.637,P=0.000)。年龄≥45岁的宫颈癌患者mTOR表达高于年龄<45岁的患者(χ^(2)=4.163,P=0.041)。临床分期Ⅲ/Ⅳ期的宫颈癌患者PI3K、Akt、mTOR表达均高于Ⅰ/Ⅱ期患者(χ^(2)=5.610,P=0.018;χ^(2)=5.450,P=0.020;χ^(2)=8.606,P=0.003)。分化程度低的宫颈癌患者PI3K、Akt、mTOR表达均高于分化程度中、高的患者(χ^(2)=7.062,P=0.029;χ^(2)=10.526,P=0.005;χ^(2)=7.714,P=0.021)。有淋巴结转移的宫颈癌患者PI3K、Akt、mTOR表达均高于无淋巴结转移的患者(χ^(2)=5.643,P=0.018;χ^(2)=6.336,P=0.012;χ^(2)=5.030,P=0.025)。不同体质指数、月经状态、肿瘤直径、组织学分类的宫颈癌患者PI3K、Akt、mTOR表达水平比较,差异均无统计学意义(P>0.05)。多因素logistic分析显示,宫颈癌患者的临床分期、分化程度、淋巴结转移均是影响PI3K、Akt、mTOR表达的独立因素(P<0.05)。PI3K、p-Akt、p-mTOR阳性患者的中位生存时间均低于阴性患者(P<0.05)。结论:宫颈癌患者中存在PI3K、Akt、mTOR的高表达,临床分期、分化程度、淋巴结转移均是影响PI3K、Akt、mTOR表达的独立因素,且高表达患者预后情况较差。

Objective:To explore the expression of protein associated with phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway in the pathological tissues of patients with cervical cancer,and to analyze the relationship between its expression level and clinical pathological parameters and prognosis of patients.Methods:The biopsy and surgical cervical cancer specimens of 61 patients with cervical cancer who were treated in The First People’s Hospital of Zunyi from January 2016 to January 2018 were collected.The expression of PI3K,p-Akt,and p-mTOR was detected by immunohistochemistry.The relationship between the expressions of PI3K,Akt,mTOR and clinicopathological characteristics of patients with cervical cancer was analyzed by multivariate logistic regression model,and the relationship between the expressions of PI3K,Akt,m TOR and prognosis of patients with cervical cancer was analyzed by Kaplan-Meier survival curve.Results:The positive rates of PI3K,p-Akt and p-m TOR in cervical cancer tissues were higher than those in para-cancerous tissues(χ^(2)=64.050,P=0.000;χ^(2)=58.607,P=0.000;χ^(2)=56.637,P=0.000).The expressions of m TOR in cervical cancer patients aged≥45 years were higher than those in patients aged<45 years(χ^(2)=4.163,P=0.041).The expressions of PI3K,Akt,and m TOR in cervical cancer patients with clinical stagesⅢandⅣwere higher than those in patients with clinical stagesⅠandⅡ(χ^(2)=5.610,P=0.018;χ^(2)=5.450,P=0.020;χ^(2)=8.606,P=0.003).The expressions of PI3K,Akt,and m TOR in cervical cancer patients with low-degree of differentiation were higher than those in patients with medium and high-degree of differentiation(χ^(2)=7.062,P=0.029;χ^(2)=10.526,P=0.005;χ^(2)=7.714,P=0.021).The expressions of PI3K,Akt and m TOR in cervical cancer patients with lymph node metastasis were higher than those in patients without lymph node metastasis(χ^(2)=5.643,P=0.018;χ^(2)=6.336,P=0.012;χ^(2)=5.030,P=0.025).There was no statistical difference in the expression levels of PI3K,Akt,and m TOR in cervical cancer patients with different body mass index,menstrual status,tumor diameter,and histological classification(P>0.05).Multivariate logistic analysis showed that the clinical stage,degree of differentiation,and lymph node metastasis of patients with cervical cancer were all independent factors influencing the expression of PI3K,Akt,and m TOR(P<0.05).The median survival time of PI3K,p-Akt,and p-m TOR positive patients were all lower than that of negative patients(P<0.05).Conclusion:There are high expressions of PI3K,Akt,and m TOR in patients with cervical cancer.Clinical stage,degree of differentiation,and lymph node metastasis are all independent factors influencing the expression of PI3K,Akt,m TOR,and the prognosis of patients with high expression is poor.