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波形蛋白表达在非小细胞肺癌中的预后价值及其临床病理意义:一项纳入4118例病例的观察性研究的荟萃分析

Prognostic Values of Vimentin Expression and Its Clinicopathological Significance in Non-Small Cell Lung Cancer: A Meta-Analysis of Observational Studies with 4118 Cases.

作者信息

Ye Zhihua, Zhang Xin, Luo Yihuan, Li Shikang, Huang Lanshan, Li Zuyun, Li Ping, Chen Gang

机构信息

Department of Pathology, First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China.

Department of Thoracic and Cardiovascular Surgery, First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China.

出版信息

PLoS One. 2016 Sep 22;11(9):e0163162. doi: 10.1371/journal.pone.0163162. eCollection 2016.

DOI:10.1371/journal.pone.0163162
PMID:27657690
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5033348/
Abstract

BACKGROUND

Vimentin is a member of the intermediate filament proteins and a canonical marker of the epithelial-mesenchymal transition (EMT), which is pivotal in tumorigenesis, metastasis and invasion in non-small cell lung cancer (NSCLC). The current meta-analysis aimed to investigate the associations between vimentin and prognosis and progression in NSCLC.

METHODS

Databases with literature published in English, including PubMed, Web of Science, Embase, Science Direct, Wiley Online Library, Ovid, Cochrane Central Register of Controlled Trials, LILACS and Google Scholar, and the CNKI, VIP, CBM and WanFang databases in Chinese were used for the literature search. The key terms included (1) 'vimentin' OR 'vim' OR 'vmt' OR 'vm' OR 'hel113' OR 'ctrct30' and (2) 'pulmon*' OR 'lung' OR 'alveolar' and (3) 'cancer' OR 'carcinoma' OR 'tumor' OR 'adenocarcinoma' OR 'squamous' OR 'neoplas*' OR 'malignan*'. The data were combined by random effect model and the H value and I2 were used to assess the heterogeneity. All the meta-analysis was conducted using Stata 12.0.

RESULTS

Thirty-two qualified studies (4118 cases) were included in the current meta-analysis. Twelve studies with 1750 patients were included to assess the significance of vimentin in the overall survival (OS) of NSCLC; the pooled hazard ratio (HR) was 1.831 (confidence interval (CI): 1.315-2.550, P<0.001) in the univariate analysis and 1.266 (CI: 0.906-1.768, P = 0.167) in the multivariate analysis. Four studies with 988 cases were applicable to determine the significance of vimentin in the disease-free survival (DFS) of NSCLC; the pooled HR of the DFS was 1.224 (CI: 0.921-1.628, P = 0.164) in the univariate analysis and 1.254 (CI: 0.985-1.956, P = 0.067) in the multivariate analysis. Regarding the relationships between vimentin and clinicopathological factors, the pooled odds ratio (OR) with 3406 NSCLCs indicated that up-regulated vimentin was associated with smoking (OR = 1.359, CI: 1.098-1.683, P = 0.004), poor differentiation (OR = 2.133, CI: 1.664-2.735, P<0.001), an advanced TNM stage (OR = 3.275, CI: 1.987-5.397, P<0.001), vascular invasion (OR = 3.492, CI: 1.063-11.472, P = 0.039), lymph node metastasis (OR = 2.628, CI: 1.857-3.718, P<0.001), recurrence (OR = 1.631, CI: 1.052-2.528, P = 0.029) and pleural invasion (OR = 2.346, CI: 1.397-3.941, P = 0.001). There was no significant correlation between vimentin and age, gender, diameter, T stage, distant metastasis, or marginal invasion (P>0.05).

CONCLUSION

An overexpression of vimentin may predict the progression and an unfavorable survival of NSCLC. Vimentin may represent a helpful biomarker and a potential target for the treatment strategies of NSCLC. Additional, prospective studies with large samples are necessary to confirm the significance of vimentin in NSCLC.

摘要

背景

波形蛋白是中间丝蛋白家族的成员,也是上皮-间质转化(EMT)的典型标志物,在非小细胞肺癌(NSCLC)的肿瘤发生、转移和侵袭过程中起关键作用。当前的荟萃分析旨在研究波形蛋白与NSCLC预后及进展之间的关联。

方法

使用英文文献发表的数据库进行文献检索,包括PubMed、Web of Science、Embase、Science Direct、Wiley Online Library、Ovid、Cochrane对照试验中心注册库、LILACS和谷歌学术,以及中文的CNKI、VIP、CBM和万方数据库。关键词包括:(1)“波形蛋白”或“vim”或“vmt”或“vm”或“hel113”或“ctrct30”;(2)“pulmon*”或“lung”或“alveolar”;(3)“cancer”或“carcinoma”或“tumor”或“adenocarcinoma”或“squamous”或“neoplas*”或“malignan*”。数据采用随机效应模型合并,并用H值和I²评估异质性。所有荟萃分析均使用Stata 12.0进行。

结果

本荟萃分析纳入了32项合格研究(4118例)。纳入12项研究共1750例患者以评估波形蛋白在NSCLC总生存期(OS)中的意义;单因素分析中合并风险比(HR)为1.831(置信区间(CI):1.315 - 2.550,P < 0.001),多因素分析中为1.266(CI:0.906 - 1.768,P = 0.167)。4项研究共988例适用于确定波形蛋白在NSCLC无病生存期(DFS)中的意义;DFS的单因素分析中合并HR为1.224(CI:0.921 - 1.628,P = 0.164),多因素分析中为1.254(CI:0.985 - 1.956,P = 0.067)。关于波形蛋白与临床病理因素的关系,纳入3406例NSCLC患者的合并比值比(OR)表明,波形蛋白上调与吸烟(OR = 1.359,CI:1.098 - 1.683,P = 0.004)、低分化(OR = 2.133,CI:1.664 - 2.735,P < 0.001)、TNM晚期(OR = 3.275,CI:1.987 - 5.397,P < 0.001)、血管侵犯(OR = 3.492,CI:1.063 - 11.472,P = 0.039)、淋巴结转移(OR = 2.628,CI:1.857 - 3.718,P < 0.001)、复发(OR = 1.631,CI:1.052 - 2.528,P = 0.029)和胸膜侵犯(OR = 2.346,CI:1.397 - 3.941,P = 0.001)相关。波形蛋白与年龄、性别、直径、T分期、远处转移或边缘侵犯之间无显著相关性(P > 0.05)。

结论

波形蛋白过表达可能预示NSCLC的进展及不良生存。波形蛋白可能是一个有用的生物标志物及NSCLC治疗策略的潜在靶点。此外,需要更多大样本前瞻性研究来证实波形蛋白在NSCLC中的意义。

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