胃癌HER-2表达与预后关系的系统评价和Meta分析

发布时间：2018-05-24 00:50

  本文选题：胃癌 + 表皮生长因子受体2　； 参考：《广西医科大学》2015年博士论文

【摘要】：目的：运用系统评价和Meta分析的方法对以往研究结果进行综合定量或定性分析,评价HER-2在胃癌中的表达分布及其表达对胃癌预后的影响。方法：根据本研究的目的,依据研究类型,研究对象,HER-2的表达情况及生存随访结果等指标制定文献的纳入及排除标准,再制定详细检索策略,通过计算机检索PUBMED数据库、EMBASE全文数据库、Cochrane Library数据库、相关期刊论文((CNKI)和万方数据库、中国生物医学文献数据库(CBM)、重庆维普中文科技期刊全文数据库(VIP)等数据库自1990年1月-2014年12月公开发表的文献。用纽卡斯尔一渥太华量表(The Newcastle-Ottawa Scale, NOS)对文献进行质量评价。建立数据收集表,收集统计HER-2表达情况对胃癌术后生存的影响,HER-2的表达分布与临床病理特征的关系等相关数据,生存资料(OS, PFS)以HR作为检验效应指标,HER-2表达分布与胃癌临床病理特征的计数资料以RR作为统计量。数据采用Revman5.3软件对提取到的资料进行统计分析,各检验效应量检验水准均采用95%可信区间(confidence interval, CI)表示。结果用森林图(Forest plot)表示。发表偏倚采用STATA12.0软件进行统计,使用Begg秩相关法和Egger回归法检验发表偏倚。结果：共纳入26篇研究文献,回顾性队列分析25篇,前瞻性队列1篇,共6529例病例,男女比例为1.86,中位年龄63.5y,分布地区有亚洲,欧洲共22国家,发表时间自1990年1月至2014年12月。HER-2表达与胃癌术后五年生存率单变量的生存分析,共纳入21篇文献,按HER-2阳性和阴性组,以五年生存率HR为指标,各研究间异质性有统计学意义,结果显示合并后HR1.75(95%CI：1.40,2.19),提示胃癌HER-2阳性患者预后差。将各研究纳入病例进行亚组分析(分别按疾病分期,HER-2检测方法,手术方式,研究地区,研究时间等因素进行分组),结果提示HER-2过表达与胃癌预后不良有关,不同的疾病分期、HER-2检测方法可能是本研究的异质性来源。8篇文献提供了多因素分析的结果,各研究间异质性有统计学意义(p=0.0007,I2=64%),使用随机效应模型,分析结果HR1.63(95%CI：1.14,1.33),提示胃癌HER-2阳性患者预后差。HER-2表达与胃癌临床病理的关系,统计结果表明,较晚的肿瘤分期RRl.43(95%CI：1.19,1.72)、肿瘤浸润较深R_R1.40(95%CI：1.08,1.82),肠型胃癌RR3.86(95%CI：2.29,6.52)、伴随淋巴结转移RR1.41(95%CI：1.18,1.70)及血管侵犯RR1.87(95%CI：1.11,3.16)的病例中存在HER-2过表达率较高,在分化较好的肿瘤中HER-2的表达则高于分化较差的肿瘤RR=0.60(95%CI：0.43,0.86)。结论：1.胃癌预后受多方面因素影响,HER-2的过表达提示胃癌预后不良。2.在较晚的肿瘤分期、肿瘤浸润较深,肠型胃癌、伴随淋巴结及血管侵犯的胃癌病例中HER-2的过表达率更高。3.本研究中由于纳入的研究文献主要为回顾性的队列分析,缺乏RCT研究,存在一定的异质性,不能完全避免偏倚,需要更多高质量的临床研究进一步验证。
[Abstract]:Objective: to evaluate the expression and distribution of HER-2 in gastric cancer and its influence on the prognosis of gastric cancer by means of systematic evaluation and Meta analysis. Methods: according to the purpose of this study, according to the type of study, the expression of HER-2 and the outcome of survival follow-up, the inclusion and exclusion criteria of literature were formulated, and the detailed retrieval strategy was worked out. The PUBMED database, the full text database of EMBASE, the database of Cochrane Library, the full text database of Chinese Journal, and the database of Wanfang are searched by computer. Chinese Biomedical Literature Database (CBMN) and Chongqing Weipu Chinese Science and Technology periodical Full-text Database (VIPB) have been published from January 1990 to December 2014. The Newcastle-Ottawa scale (NOS) was used to evaluate the quality of the literature. A data collection table was established to collect the data related to the relationship between the expression distribution of HER-2 and the clinicopathological characteristics of gastric cancer. Survival data (OS, PFS): HR was used as the test index of HER-2 expression and the count of clinicopathological features of gastric cancer was measured by RR. The data were statistically analyzed by Revman5.3 software, and the test level of each test effect quantity was expressed by 95% confidence intervalency (CI). The results are expressed in forest maps. Publication bias was analyzed by STATA12.0 software, and Begg rank correlation method and Egger regression method were used to test publication bias. Results: a total of 26 literatures were included, including 25 retrospective cohort analysis, 1 prospective cohort, 6529 cases, the ratio of male to female was 1.86, the median age was 63.5 y.The distribution region was Asia and 22 countries in Europe. From January 1990 to December 2014, the expression of HER-2 and the survival rate of five years after operation were analyzed by univariate analysis. A total of 21 articles were included. According to the HER-2 positive and negative groups, the 5-year survival rate HR was used as the index. There was significant difference in the heterogeneity among the various studies. The results showed that the prognosis of patients with HER-2 positive gastric cancer was poor after HR1.75 / 95 CI: 1.40 / 2.19%. Subgroup analysis was carried out in each study (HER-2 detection method, surgical method, study area, study time, etc.). The results showed that the overexpression of HER-2 was associated with poor prognosis of gastric cancer. Different HER-2 detection methods may be the result of multivariate analysis provided by 8 articles of heterogeneity source of this study. The heterogeneity of each study has statistical significance (P < 0. 0007 / I ~ 2 / 64), using random effect model. The results showed that the expression of HER-2 in patients with HER-2 positive gastric cancer was related to the clinicopathology of gastric cancer. In the later stage, RRl.43995 CIV: 1.191.72a, RR1.4095CI1.081.82, RR3.8695CIW 2.2996.52, with lymph node metastasis RR1.4195 CIV: 1.181.70) and vascular invasion RR1.8795 CIW 1.111.113.16), the overexpression rate of HER-2 was higher, and the expression of HER-2 in well-differentiated tumor was higher than that in well-differentiated tumor. The expression of HER-2 in well-differentiated tumor was higher than that in poorly differentiated tumor. Conclusion 1. The overexpression of HER-2 suggests that the prognosis of gastric cancer is poor. 2. The overexpression rate of HER-2 was higher in gastric carcinoma with lymph node and vascular invasion than in the later stage with deep invasion of tumor and intestinal type of gastric cancer. Because the research literature included in this study is mainly retrospective cohort analysis, the lack of RCT research, there is a certain heterogeneity, can not completely avoid bias, need more high-quality clinical research to further verify.
【学位授予单位】：广西医科大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R735.2
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本文编号：1927051