P53状态与食管鳞癌预后及临床病理特征关系的系统评价

Relationship between P53 status and prognosis and clinicopathologic characteristics in esophagus squamous cell carcinoma:A systematic review

目的:系统评价p53基因突变和/或蛋白表达异常对食管鳞癌预后影响及其与临床病理特征之间的关系.方法:系统检索Pub Med、SCI-Ex-panded、EMBASE、Cochrane图书馆、中国期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、维普中文科技期刊数据库(VIP);并追踪已获文献的参考文献.纳入有关的临床对照研究.根据预先设定的纳入和排除标准,2名研究者独立对文献进行筛选及数据提取.根据Newcastle-Ottawa scale(NOS)标准对文献质量进行评估;采用Revman5.3软件进行发表偏倚评估及数据综合;根据异质性的大小采用固定或随机效应模型.结果:共有85项研究(8825例)符合纳入标准,p53基因突变、P53蛋白表达异常4608例(研究组),P53野生型/蛋白表达阴性4217例(对照组).纳入研究两组间OS的风险比(hazard ratio,HR)为1.35(95%CI:1.23-1.47,P<0.00001,异质性P=0.39,I^2=5%);两组间5年生存率的危险比(risk ratio,RR)为0.73(95%CI:0.62-0.87,P=0.0003,异质性P=0.001,I^2=50%);3年生存率的RR值为0.87(95%CI:0.74-1.02,P=0.09,异质性P=0.28,I^2=18%).P53突变/蛋白表达异常的食管鳞癌的T分期(RR=1.09,P=0.004)、N分期(RR=1.24,P<0.00001)、M分期(RR=1.65,P<0.00001)、TNM分期(RR=1.25,P<0.00001)更晚,分化程度(RR=1.06,P=0.03)更差;而P53状态与肿瘤的血管侵犯、位置、大小及患者年龄、性别间无明显相关性(均P>0.05).结论:P53突变/蛋白表达异常是食管鳞癌预后不良的标志物之一.同时,P53突变/蛋白表达异常的患者较对照组肿瘤浸润深度更深、淋巴结及远处转移率更高、TNM分期更晚、分化程度更差.

AIM： To evaluate the prognostic role of p53 status and its relationship with clinicopathologic characteristics in esophagus squamous cell carcinoma （ESCC）. METHODS： A systematic search of PubMed, SCI-Ex-panded, EMBASE, the Cochrane library, China National Knowledge Infrastructure （CNKI）, Chinese Biomedical Database （CBM）, and science and technology periodical database （VIP） was performed. Related references were also searched for additional clinical studies. Two reviewers independently performed screening of identified studies and data extracting according to inclusion and exclusion criteria. The quality assessment was conducted on the basis of the Newcastle-Ottawa Quality Assessment Scale （NOS）. The evaluation of the publication bias of the included studies and data synthesis were performed with RevMan 5.3. A fixed-effect or random effects model was adopted according to heterogeneity.survival rates was 0.73 （95%CI： 0.62-0.87, P = 0.0003; heterogeneity： P = 0.001, 12= 50%） and 0.87 （95%CI： 0.74-1.02, P = 0.09; heterogeneity： P = 0.28, 12 = 18%）. p53 gene mutation or protein expression was significantly associated with poorer T stage （RR = 1.09, P = 0.004）, N stage （RR = 1.24, P 〈 0.00001）, M stage （RR = 1.65, P 〈 0.00001）, TNM stage （RR = 1.25, P 〈 0.00001） and differentiation degree （RR = 1.06, P = 0.03）. However, there were no association between P53 status and vascular invasion, tumor location, size, age or gender in ESCC （P 〉 0.05）. CONCLUSION： p53 gene mutation or protein expression abnormality is a marker of poor prognosis in patients with ESCC. Meantime, patients with P53 abnormalities are associated with higher depth of invasion, higher rate of lymph node metastasis and distant metastasis, later TNM stage, and poorer grade of differentiation.