PTTG和p21作为无功能垂体瘤放射治疗预后的分子标志物

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (9): 1253-1259.

PTTG和p21作为无功能垂体瘤放射治疗预后的分子标志物

李阳芳^1,2, 胡慧敏^1,2*

1.北京市神经外科研究所,北京 100070;
2.首都医科大学附属北京天坛医院神经外科,北京 100070

收稿日期:2020-11-10 修回日期:2021-01-24 出版日期:2021-09-05 发布日期:2021-09-02
通讯作者: *huhm_bjni@163.com
基金资助:
国家自然科学基金(81972816)

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

LI Yang-fang^1,2, HU Hui-min^1,2*

1. Beijing Neurosurgical Institute, Beijing 100070;
2. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China

Received:2020-11-10 Revised:2021-01-24 Online:2021-09-05 Published:2021-09-02
Contact: *huhm_bjni@163.com

摘要/Abstract

摘要： 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。

关键词: 垂体瘤转化基因(PTTG), 细胞周期依赖性激酶抑制剂1A(p21), 组织芯片, 放射治疗耐受

Abstract: 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.

Key words: pituitary tumor transforming gene(PTTG), cycle-dependent kinase inhibitor 1A(p21), tissue microarray, radiation resistance

中图分类号:

李阳芳, 胡慧敏. PTTG和p21作为无功能垂体瘤放射治疗预后的分子标志物[J]. 基础医学与临床, 2021, 41(9): 1253-1259.

LI Yang-fang, HU Hui-min. PTTG and p21 as prognostic biomarker in radiotherapy for non-functional pituitary adenomas[J]. Basic & Clinical Medicine, 2021, 41(9): 1253-1259.

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