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联合检测前列腺癌组织Notch1、FLNA表达的临床意义
作者:马阔  李泽宇  刘沛  韩广业 
单位:新乡医学院第一附属医院 泌尿外科, 河南 新乡 453100
关键词:前列腺癌 缺刻基因1 细丝蛋白A 临床特征 预后 
分类号:R737.25
出版年·卷·期(页码):2025·44·第一期(30-37)
摘要:

目的:分析前列腺癌组织缺刻基因1(Notch1)和细丝蛋白A(FLNA)的表达水平与临床病理特征的关系及其对预后的预测价值。方法:收集2018年7月到2020年12月在本院接受根治性手术的112例前列腺癌患者为研究对象,根据预后情况分为预后良好组(79例)和预后不良组(33例)。采用免疫组化法测定前列腺癌和癌旁组织中Notch1蛋白和FLNA的表达情况;实时荧光定量PCR(qPCR)法检测组织中Notch1 mRNA和FLNA mRNA表达水平;Kaplan-Meier生存曲线分析Notch1 mRNA、FLNA mRNA表达水平与患者预后生存率关系;绘制受试者工作特征(ROC)曲线分析前列腺癌组织中Notch1 mRNA和FLNA mRNA表达对患者预后的预测效能。结果:前列腺癌组织Notch1蛋白阳性率为81.25%,高于癌旁组织的21.43%(P<0.05);FLNA阳性率为20.54%,低于癌旁组织的77.68%(P<0.05)。前列腺癌组织Notch1 mRNA、FLNA mRNA表达水平与患者年龄、Gleason评分、微血管侵犯、包膜侵犯、精囊侵犯、神经周围侵犯、手术切缘阳性、TNM分期和前列腺特异性抗原(PSA)有关(P<0.05)。与预后良好组(Notch1 mRNA=1.45±0.29,FLNA mRNA=0.87±0.17)相比,预后不良组患者前列腺癌组织中Notch1 mRNA(2.01±0.44)表达水平升高(P<0.05),FLNA mRNA(0.68±0.13)表达水平下降(P<0.05)。前列腺癌患者3年生存率为70.54%(79/112),Notch1 mRNA高表达组患者3年生存率(55.17%)低于低表达组(87.04%)(Log-rank χ2=14.492,P<0.001),FLNA mRNA高表达组3年生存率(82.46%)高于低表达组(58.18%)(Log-rank χ2=8.532,P=0.003)。ROC曲线结果显示前列腺癌组织Notch1 mRNA和FLNA mRNA联合预测预后的AUC为0.874,显著大于Notch1 mRNA(Z=2.035,P=0.042)和FLNA mRNA(Z=2.270,P=0.023)单独预测。结论:前列腺癌组织Notch1蛋白阳性率高于癌旁组织,FLNA阳性率低于癌旁组织,两者与患者临床特征和预后具有相关性,两者mRNA联合检测对患者预后预测效能较高。

Objective: To analyze the expression levels of Notch1 gene and Filamin A(FLNA) protein in prostate cancer tissue and their relationship with clinical pathological features and predictive value for prognosis. Methods:A total of 112 prostate cancer patients who underwent radical surgery from July 2018 to December 2020 were collected as research subjects and divided into a good prognosis group of 79 cases and a poor prognosis group of 33 cases according to the prognosis. Immunohistochemistry was used to determine the expression of Notch1 protein and FLNA in prostate cancer and adjacent tissues; real-time fluorescence quantitative PCR(qPCR) was used to detect the expression levels of Notch1 mRNA and FLNA mRNA in tissues; Kaplan-Meier survival curves were used to analyze the relationship between the expression levels of Notch1 mRNA and FLNA mRNA and the patients' prognosis survival rate; the receiver operating characteristic(ROC) curve was plotted to analyze the predictive efficacy of Notch1 mRNA and FLNA mRNA expression in prostate cancer tissue for patients' prognosis. Results:The positive rate of Notch1 protein in prostate cancer tissues(81.25%) was higher than that in adjacent tissues(21.43%), and the positive rate of FLNA(20.54%) was lower than that in adjacent tissues(77.68%)(P<0.05). The expression levels of Notch1 mRNA and FLNA mRNA in prostate cancer tissues were related to age, Gleason score, microvascular invasion, capsule invasion, seminal vesicle invasion, perineural invasion, positive surgical margin, TNM stage and prostate-specific antigen(PSA)(P<0.05). Compared with the good prognosis group(Notch1 mRNA=1.45±0.29, FLNA mRNA=0.87±0.17), the expression level of Notch1 mRNA(2.01±0.44) in prostate cancer tissues of the poor prognosis group was increased(P<0.05), FLNA mRNA(0.68±0.13) decreased(P<0.05); the 3-year survival rate of prostate cancer patients was 70.54%(79/112), and the 3-year survival rate of patients with high expression of Notch1 mRNA(55.17%) was lower than that of the low expression group(87.04%)(Log-rank χ2=14.492, P<0.001); the 3-year survival rate of the high expression group of FLNA mRNA(82.46%) was higher than that of the low expression group(58.18%)(Log-rank χ2=8.532, P=0.003). The ROC curve results showed that the AUC for the combined prediction of prognosis by Notch1 mRNA and FLNA mRNA in prostate cancer tissue was 0.874, which was significantly greater than those predicted by Notch1 mRNA(Z=2.035, P=0.042) and FLNA mRNA alone(Z=2.270, P=0.023). Conclusion: The positive rate of Notch1 protein in cancer tissues of prostate cancer patients is higher than that in adjacent tissues, and the positive rate of FLNA is lower than that in adjacent tissues. The two are correlated with the clinical characteristics and prognosis of patients, and the combined detection of Notch1 mRNA and FLNA mRNA has a high predictive efficiency for the prognosis of patients.

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