p-mTOR蛋白在结直肠癌组织中的表达及患者预后判断中的价值

doi:10.3969/j.issn.1004-616x.2020.03.001

癌变·畸变·突变 ›› 2020, Vol. 32 ›› Issue (3): 161-165.doi: 10.3969/j.issn.1004-616x.2020.03.001

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p-mTOR蛋白在结直肠癌组织中的表达及患者预后判断中的价值

朱依青¹, 张彤彤^1,2, 郑珺文¹, 郝佳洁¹, 蔡岩¹, 王明荣¹, 梁建伟³, 张钰¹

1. 国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院, 分子肿瘤学国家重点实验室, 北京 100021;
2. 成都市第三人民医院实验医学研究部, 四川成都 610031;
3. 国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院, 结直肠外科, 北京 100021

收稿日期:2020-01-13 修回日期:2020-04-11 出版日期:2020-05-31 发布日期:2020-06-03
通讯作者: 梁建伟,E-mail:liangjw1976@126.com;张钰,E-mail:zhangyu909@126.com E-mail:liangjw1976@126.com;zhangyu909@126.com
作者简介:朱依青,E-mail:15602180441@163.com。
基金资助:
国家自然科学基金（81472562，81441070）；国家重点研发计划（2016YFC0905301）；中国医学科学院医学与健康科技创新工程（2017-I2M-1-006）

Expression status of p-mTOR and its prognostic implication in colorectal cancer

ZHU Yiqing¹, ZHANG Tongtong^1,2, ZHENG Junwen¹, HAO Jiajie¹, CAI Yan¹, WANG Mingrong¹, LIANG Jianwei³, ZHANG Yu¹

1. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021;
2. Medical Research Center, The Third People's Hospital of Chengdu, Chengdu 610031, Sichuan;
3. Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

Received:2020-01-13 Revised:2020-04-11 Online:2020-05-31 Published:2020-06-03

摘要/Abstract

摘要： 目的：检测p-mTOR（Ser2448，活化形式的mTOR）蛋白在结直肠癌中的表达变化并评价其用于判断患者预后的价值。方法：采用组织芯片-免疫组织化学染色技术，检测441例结直肠癌及其配对癌旁正常组织中p-mTOR的表达，收集患者至少5年的随访信息，并分析其表达水平与临床病理指标及患者预后的相关性。结果：免疫组织化学染色结果显示p-mTOR在癌旁正常结直肠上皮细胞中阳性表达率为4%（17/441），而在结直肠癌组织中阳性表达率为58%（254/441），两者间差异显著（P < 0.01）。统计分析结果显示，在结直肠癌组织中，p-mTOR的表达水平与肿瘤分级、淋巴结转移、远处转移及病理分期显著正相关（P均 < 0.05）。同时，p-mTOR的表达水平与结直肠癌患者的预后显著相关（P均 < 0.05），p-mTOR高表达患者的无病生存期和总生存期分别为52和60个月，明显短于p-mTOR低表达患者的71和70个月。Cox多因素分析结果显示p-mTOR表达水平为结直肠癌患者的独立预后因素。结论：p-mTOR在结直肠癌组织中表达上调，其高表达与结直肠癌患者预后不良相关，有可能作为预测结直肠癌患者术后死亡及复发转移风险的候选分子标志物。

关键词: 结直肠癌, p-mTOR, 预后标志物, 无病生存率, 总生存率

Abstract: OBJECTIVE: To investigate expression status of p-mTOR(Ser2448,an active form of mTOR)in colorectal cancer (CRC),and its correlation with clinicopathological features and prognosis. METHODS: Protein expression of p-mTOR was examined using the tissue microarrays-immunohistochemistry (TMA-IHC) technique in surgically-resected colorectal cancer tissues and adjacent normal epithelia from 441 patients. Correlations between p-mTOR expression levels,clinicopathological parameters and prognosis of patients were analyzed using the Pearson Chi-square and Fisher exact tests,and Kaplan-Meier survival and Cox regression analyses. RESULTS: Overexpression of p-mTOR was detected in 58% (254/441) of the CRC specimens but only 4% (17/441) of the normal colorectal epithelia,and the difference between them was significant (P < 0.01). In addition,elevated p-mTOR expression was positively correlated with higher pathologic T stage,lymph node metastasis,distant metastasis,and advanced clinical stage (each P < 0.05). Kaplan-Meier survival analysis showed the expression level of p-mTOR was significantly correlated with the poor prognosis of colorectal cancer patients (each P < 0.05). The disease-free survival (DFS) and overall survival (OS) of patients with high expression of p-mTOR were 52 and 60 months,respectively,which were significantly shorter than those with low expression of p-mTOR (71 and 70 months). The Cox multiple regression analyses reveal that p-mTOR overexpression was an independent prognostic factor for DFS and OS in CRC patients. CONCLUSION: p-mTOR was frequently upregulated in CRC,and its overexpression was significantly correlated with adverse outcomes;thus,it may serve as a potential prognostic marker for predicting the risk of postoperative death,recurrence and metastasis in patients with colorectal cancer.

Key words: colorectal cancer, phospho-mammalian/mechanistic target of rapamycin, prognostic biomarker, disease-free survival rate, overall survival rate

中图分类号:

R730.7

朱依青, 张彤彤, 郑珺文, 郝佳洁, 蔡岩, 王明荣, 梁建伟, 张钰. p-mTOR蛋白在结直肠癌组织中的表达及患者预后判断中的价值[J]. 癌变·畸变·突变, 2020, 32(3): 161-165.

ZHU Yiqing, ZHANG Tongtong, ZHENG Junwen, HAO Jiajie, CAI Yan, WANG Mingrong, LIANG Jianwei, ZHANG Yu. Expression status of p-mTOR and its prognostic implication in colorectal cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(3): 161-165.

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p-mTOR蛋白在结直肠癌组织中的表达及患者预后判断中的价值

Expression status of p-mTOR and its prognostic implication in colorectal cancer

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