PTEN蛋白缺失与中国前列腺癌患者根治术后生化复发风险关系的研究

PTEN protein loss is associated with an increased risk of recurrence in Chinese patients after prostatectomy for clinically localized prostate cancer

背景与目的:张力蛋白同源第10号染色体缺失的磷酸酶基因(phosphatase and tensin homolog deleted on chromosome 10,PTEN)缺失是西方国家前列腺癌中最常见的基因异常之一,与肿瘤的进展、预后均有一定相关性。鉴于前列腺癌的异质性,不同地区、人群间其基因表达谱存在广泛差异,本研究主要探讨PTEN蛋白缺失在中国前列腺癌患者中的发生率以及与生化复发的相关性。方法:选取2006—2011年225例局限性前列腺癌并采取根治切除术的患者为研究对象,回顾性收集所有患者的临床病理资料,包括确诊时年龄、血清前列腺特异性抗原(prostate-specific antigen,PSA)值、Gleason分级评分、TNM分期、手术切缘和术后生化复发与否及时间。将225例局限性前列腺癌根治切除标本的肿瘤组织及癌旁组织制成组织芯片(tissue microarray,TMA),采用免疫组织化学技术检测PTEN蛋白在肿瘤及癌旁组织中的表达。采用χ2检验分析前列腺癌组织中PTEN蛋白缺失与患者临床病理特征的相关性。运用Kaplan-Meier生存分析模型、Cox比例风险模型分析PTEN蛋白缺失及患者临床病理特征与生化复发的关系。结果:前列腺癌患者中PTEN蛋白缺失率为15%(33/217),且存在PTEN蛋白缺失的前列腺癌患者其确诊时血清PSA值(P=0.030)及年龄(P=0.009)要显著高于PTEN表达的前列腺癌患者。单因素生存分析显示,PTEN表达情况(P=0.013 1)、确诊时血清PSA值(P=0.000 4)和Gleason分级评分(P=0.019 8)与前列腺癌患者的生化复发相关。Cox多因素分析结果表明,PTEN蛋白表达情况(HR=0.536,P=0.044)、确诊时血清PSA值(HR=1.879,P=0.001)和Gleason分级评分(HR=1.361,P=0.030)为前列腺癌患者生化复发的独立预后因素。结论:PTEN蛋白表达情况是局限性前列腺癌患者根治术后生化复发的独立预后因素,检测PTEN蛋白有望改善根治术后前列腺癌患者的管理及指导进一步治疗。

Background and purpose：Loss of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 （PTEN） is one of the most common somatic genetic aberrations in prostate cancer in Western countries and is frequently associated with tumor progression and poor prognosis. This study aimed to investigate the frequency of PTEN protein loss in Chinese prostate cancer patients and to determine its association with the biochemical recurrence of prostate cancer.Methods：The data from 225 diagnosed localized prostate cancer patients with radical prostatectomy from 2006 to 2011 were collected retrospectively, including patient’s age at diagnosis, prostate-speciifc antigen （PSA） level at diagnosis, Gleason score, clinical stage, surgical margin, and time to biochemical recurrence or not. This study performed PTEN protein immunohistochemistry on tissue microarrays, which were made from 225 Chinese prostate cancer patients mentioned above, treated by radical prostatectomy with one case including 2 cancer spots and 2 adjacent normal gland spots. Correlations of PTEN loss with clinicopathological features were analyzed usingχ2 test. Kaplan-Meier survival model and Cox proportional hazards regression model were used to evaluate the predictive role of PTEN protein expression and patient characteristics for biochemical recurrence. Results：PTEN protein loss was observed in 15% of the patients and was associated with increased preoperative PSA levels （P=0.03） and old age （P=0.009）. In univariate Kaplan–Meier analysis, the factors associated with the biochemical recurrence of prostate cancer included PSA levels （P=0.000 4）, Gleason sum （P=0.019 8）, and PTEN status （P=0.013 1）. In multivariable Cox regression analysis, PTEN expression （HR=0.536, P=0.044）, PSA levels （HR=1.879, P=0.001）, and Gleason score （HR=1.361,P=0.03） were signiifcant in predicting biochemical recurrence of prostate cancer.Conclusion：PTEN protein loss is associated with an increased risk of recurrence, independent of known clinicopathological factors.