發(fā)布時間：2018-05-24 00:50

  本文選題：胃癌 + 表皮生長因子受體2　； 參考：《廣西醫(yī)科大學》2015年博士論文

【摘要】：目的：運用系統(tǒng)評價和Meta分析的方法對以往研究結(jié)果進行綜合定量或定性分析,評價HER-2在胃癌中的表達分布及其表達對胃癌預后的影響。方法：根據(jù)本研究的目的,依據(jù)研究類型,研究對象,HER-2的表達情況及生存隨訪結(jié)果等指標制定文獻的納入及排除標準,再制定詳細檢索策略,通過計算機檢索PUBMED數(shù)據(jù)庫、EMBASE全文數(shù)據(jù)庫、Cochrane Library數(shù)據(jù)庫、相關期刊論文((CNKI)和萬方數(shù)據(jù)庫、中國生物醫(yī)學文獻數(shù)據(jù)庫(CBM)、重慶維普中文科技期刊全文數(shù)據(jù)庫(VIP)等數(shù)據(jù)庫自1990年1月-2014年12月公開發(fā)表的文獻。用紐卡斯爾一渥太華量表(The Newcastle-Ottawa Scale, NOS)對文獻進行質(zhì)量評價。建立數(shù)據(jù)收集表,收集統(tǒng)計HER-2表達情況對胃癌術后生存的影響,HER-2的表達分布與臨床病理特征的關系等相關數(shù)據(jù),生存資料(OS, PFS)以HR作為檢驗效應指標,HER-2表達分布與胃癌臨床病理特征的計數(shù)資料以RR作為統(tǒng)計量。數(shù)據(jù)采用Revman5.3軟件對提取到的資料進行統(tǒng)計分析,各檢驗效應量檢驗水準均采用95%可信區(qū)間(confidence interval, CI)表示。結(jié)果用森林圖(Forest plot)表示。發(fā)表偏倚采用STATA12.0軟件進行統(tǒng)計,使用Begg秩相關法和Egger回歸法檢驗發(fā)表偏倚。結(jié)果：共納入26篇研究文獻,回顧性隊列分析25篇,前瞻性隊列1篇,共6529例病例,男女比例為1.86,中位年齡63.5y,分布地區(qū)有亞洲,歐洲共22國家,發(fā)表時間自1990年1月至2014年12月。HER-2表達與胃癌術后五年生存率單變量的生存分析,共納入21篇文獻,按HER-2陽性和陰性組,以五年生存率HR為指標,各研究間異質(zhì)性有統(tǒng)計學意義,結(jié)果顯示合并后HR1.75(95%CI：1.40,2.19),提示胃癌HER-2陽性患者預后差。將各研究納入病例進行亞組分析(分別按疾病分期,HER-2檢測方法,手術方式,研究地區(qū),研究時間等因素進行分組),結(jié)果提示HER-2過表達與胃癌預后不良有關,不同的疾病分期、HER-2檢測方法可能是本研究的異質(zhì)性來源。8篇文獻提供了多因素分析的結(jié)果,各研究間異質(zhì)性有統(tǒng)計學意義(p=0.0007,I2=64%),使用隨機效應模型,分析結(jié)果HR1.63(95%CI：1.14,1.33),提示胃癌HER-2陽性患者預后差。HER-2表達與胃癌臨床病理的關系,統(tǒng)計結(jié)果表明,較晚的腫瘤分期RRl.43(95%CI：1.19,1.72)、腫瘤浸潤較深R_R1.40(95%CI：1.08,1.82),腸型胃癌RR3.86(95%CI：2.29,6.52)、伴隨淋巴結(jié)轉(zhuǎn)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過表達率較高,在分化較好的腫瘤中HER-2的表達則高于分化較差的腫瘤RR=0.60(95%CI：0.43,0.86)。結(jié)論：1.胃癌預后受多方面因素影響,HER-2的過表達提示胃癌預后不良。2.在較晚的腫瘤分期、腫瘤浸潤較深,腸型胃癌、伴隨淋巴結(jié)及血管侵犯的胃癌病例中HER-2的過表達率更高。3.本研究中由于納入的研究文獻主要為回顧性的隊列分析,缺乏RCT研究,存在一定的異質(zhì)性,不能完全避免偏倚,需要更多高質(zhì)量的臨床研究進一步驗證。
[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.
【學位授予單位】：廣西醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R735.2
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本文編號：1927051