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学科主题: 肿瘤学
题名:
P21、COX-2、E-cadherin可作为ESCC患者的预后分子----附153例ESCC验证
作者: 林瑶
答辩日期: 2016-05-25
导师: 陈克能
专业: 肿瘤学
授予单位: 北京大学
授予地点: 北京大学临床肿瘤学院
学位: 硕士
关键词: 食管鳞状细胞癌 ; 预后 ; 免疫组化
其他题名: P21, COX-2, and E-cadherin are potential prognostic factors for esophageal squamous cell carcinoma---validation with 153 cases
分类号: R735.1
摘要:

背景与目的:食管鳞癌是我国的常见病与多发病,其主要治疗方式是外科切除。TNM分期是食管鳞癌标准的分期系统,其在很大程度上能够正确地指导治疗以及判断预后,然而,在实际临床工作中,常常出现预后与分期不符的现象,这就使得人们开始寻找除TNM分期之外的对食管鳞癌预后有影响的因素,其中最受关注的便是分子标志物。我们在上一部分研究中回顾性总结了北京大学肿瘤医院单中心临床上曾选用的免疫分子指标,并在胸外一科单一手术组接受单纯手术治疗的食管鳞癌患者中进行验证,结果发现除了PCNA的表达与本组患者预后显著相关外,其余各指标的表达均未发现与食管鳞癌患者的预后显著相关。因此,本研究的目的即是从文献回顾的角度,从数以千计的基础及转化研究中整理总结出目前最受关注的食管鳞癌预后分子标志物,并在我们随访良好的前瞻性数据库中进行验证,以期为未来更大样本量的前瞻性研究及临床实践提供一定参考。

方法:在PubMed数据库中以“食管鳞癌”、“免疫组化“及
“预后“为关键词,检索在1960年~2015年间发表的有关食管鳞癌预后标志物的文章,并采用如下标准对纳入的文献进行筛选:1、文献发表的时间为1980年-2015年;2、病理明确为ESCC;3、采用了Kaplan-Meier 和Log-Rank 检验进行单因素分析或者采用COX 风险比例回归模型进行多因素分析;4、样本量大于100;5、≥3项研究报道,至少有一项研究表明该蛋白的表达是影响预后的因素;6、发表期刊被SCI收录。将文献回顾所挑选出来的最受关注的指标在我们严格随访的前瞻性数据库中进行验证,将2000年~2010年单中心食管鳞癌单一手术患者作为验证组,共153例。采用SPSS 18.0软件进行统计分析。

结果:按照关键词搜索到1799篇文献,按筛选标准共82篇文献符合要求。检索到与预后相关的免疫组化分子共12个,分别是:P53、CyclinD1 、E-cadherin 、VEGF 、HER-2、P21 、EGFR、COX2、P27、P16、Ki-67、Survivin。其中,Survivin与患者的TNM分期正相关(P=0.029),Ki-67与肿瘤的分化程度负相关(P=0.012),COX-2与肿瘤的分化程度负相关(P=0.025),与TNM分期(P=0.011)正相关。其余指标与患者各临床因素之间未发现显著相关关系。单因素分析发现P21、COX-2和E-cadherin的表达与食管鳞癌患者预后相关,且P21低表达者生存时间明显短于高表达者(5年生存率分别为32.1%与56.7%);E-cadherin高表达者明显短于低表达者(5年生存率分别为40.2%与64.5%);COX-2高表达者生存时间也短于低表达者(5年生存率分别为40.2%与64.2%)。其余指标的表达与本组患者的总生存间均无明显相关性。多因素分析结果显示,P21低表达(HR(95% CI )=1.71(1.02~2.87))、E-cadherin高表达(HR(95% CI )=1.91(1.02~3.57))和COX-2高表达(HR(95% CI )=1.93(1.08~3.44))均是ESCC患者的独立预后危险因素。

结论:Survivin和COX-2的表达与食管鳞癌患者的TNM分期正相关,Ki-67和COX-2的表达与肿瘤的分化程度负相关。同时,P21、COX-2和E-cadherin的表达有可能成为接受单一手术治疗的食管鳞癌患者预后的分子标记物,但要真正将此结果应用于临床,尚需进一步的前瞻性研究及大样本量的验证。

英文摘要:

Background and Objective: Esophageal squamous cell carcinoma(ESCC) is a common and frequently occurring disease in China with the major treatment being resection. TNM staging system, which has played an important role in treatment guiding and prognosis predicting, is currently the standard staging system for ESCC. However, in clinical practice, the patients’ prognosis are not always consistent with staging, and this lead to the exploration of other prognostic markers than TNM deors, among which molecular biomarkers were the most concerned. In fact, there are hundreds and thousands publications on prognostic biomarkers for ESCC, however, to date there is no confirmed findings. We hypothesized that certain molecules found in previous studies could act as prognostic markers for ESCC. The current study, therefore, aimed to validate the most concerned markers in our prospective esophageal cancer database.

Methods: A literature search was performed using the PubMed database for papers published between 1960 and 2015 using the following key words: ‘esophageal cancer’, ‘prognosis’ and ‘immunohistochemistry’. The following literature ion criteria were made to identify the most widely researched markers, including: 1. The publication time ranges from 1960 to 2015; 2. Pathologically diagnosis of squamous cell carcinoma; 3. Kaplan-Meier curve and Log-Rank test were used to conducte univariate analysis and COX proportional hazard model was carried out for multivariate analysis. 4. The sample size more than 100; 5. At least 3 publications studied, and at least one study demonstrated that the protein was significant prognostic biomarker for ESCC; 6. The researches were published in SCI journals. Next, we validated the ed markers from literature review in our single surgeon team with 153 esophageal cancer patients from 2000 to 2010. SPSS 18.0 software was applied for all statistical analysis.

Results: A total of 1799 articles were identified, with 82 met the ion criteria. The following twelve markers were found to be the most widely researched: P53, CyclinD1, E-cadherin, VEGF, HER-2, P21, EGFR, COX2, P27, P16, Ki-67 and Survivin. Among the twelve markers, survivin was found to the associated with TNM staging(p=0.029), Ki-67 was found to be associated with tumor differentiation(p=0.012), COX-2 was found to be negatively associated with tumor differentiation(p=0.025) and positively associated with TNM staging(p=0.011). Other biomarkers were not found to be significantly correlated with pathients’ clinicopathological acteristics. In addition, P21, COX-2 and E-cadherin were found to be independent prognostic factors for ESCC patients in this series.

Conclusions: The systemic review and cohort validation paved the way for P21, COX-2 and E-cadherin as potential prognostic factors for ESCC and more targeted prospective validation in the future.

语种: 中文
相关网址: 查看原文
内容类型: 学位论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/125692
Appears in Collections:北京大学临床肿瘤学院_学位论文

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作者单位: 北京大学临床肿瘤学院

Recommended Citation:
林瑶. P21、COX-2、E-cadherin可作为ESCC患者的预后分子----附153例ESCC验证[D]. 北京大学临床肿瘤学院. 北京大学. 2016.
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