PTTG和p21作为无功能垂体瘤放射治疗预后的分子标志物

PTTG and p21 as prognostic biomarker in radiotherapy for non-functional pituitary adenomas

目的研究垂体瘤转化基因(PTTG)和细胞周期依赖性激酶抑制剂1A(p21)蛋白表达对无功能垂体瘤(NFPAs)患者放射治疗(简称放疗)预后的预测作用。方法收集2003年至2013年垂体瘤手术后并行伽马刀放射外科治疗(GKRS)的患者,共计89例样本。根据GKRS时间分为研究组和验证组;依据随访磁共振影像,肿瘤体积缩小≥20%的被认作放疗敏感;利用组织芯片(TMA)检测14种蛋白标志物在NFPAs中的表达。结果无论研究组还是验证组,COX回归分析显示细胞核PTTG(HR:1.355;P<0.05或HR:1.637;P<0.01)和细胞质p21(HR:1.174;P<0.01或HR:1.378;P<0.01)的高表达与放射治疗耐受显著相关;在研究组,卡普兰迈耶(KM)曲线分析显示PTTG核阴性(P<0.01)和p21细胞质低表达(P<0.01)的患者,具有更高的放疗敏感性,并在验证组中得到了印证(PTTG,P<0.05;p21,P<0.01)。结论细胞核PTTG或细胞质p21表达升高的NFPAs患者,更倾向于放射治疗耐受;PTTG和p21是预测NFPAs放射治疗效果的潜在分子标志物。

Objective To evaluate the predictive value of pituitary tumor transforming gene(PTTG)and cycle-dependent kinase inhibitor 1A(p21)in the prognosis of pituitary adenomas underwent radiotherapy.Methods A total of 89 postoperative patients with non-functional pituitary adenomas(NFPAs)treated by gamma knife radiosurgery(GKRS)from 2003 to 2013 were collected.The cases were divided into research and validation cohorts based on the radiosurgery operation time.According to the follow-up MRI,a decrease of tumor more than 20%was defined as radiosensitive;Expression of sixteen protein markers in pituitary adenomas was determined using a tissue microarray.Results Univariate analysis revealed that nucleus positive PTTG(HR:1.355;P<0.05 or HR:1.637;P<0.01)and cytoplasm high expression of p21(HR:1.174;P<0.01 or HR:1.378;P<0.01)were significantly correlated with radiation resistance in both research and validation group.In the research group,Kaplan Meyer(KM)curve analysis showed patients with nucleus negative PTTG(P<0.01)and cytoplasm low expression of p21(P<0.01)had a higher radiosensitivity,the same results were obtained in the validation group(PTTG,P<0.05;p21,P<0.01).Conclusions Patients with nucleus positive PTTG and cytoplasm high expression of p21 tend to be resistant to radiotherapy in pituitary adenomas;PTTG and p21 are prognostic protein markers associated with radiation resistance.