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中华普通外科学文献(电子版) ›› 2018, Vol. 12 ›› Issue (02) : 139 -144. doi: 10.3877/cma.j.issn.1674-0793.2018.02.018

所属专题： 文献；

循证医学

长链非编码RNA低表达与胃癌患者预后关系的Meta分析
龙勃1, 王科深1, 任彦先1, 马志坚1, 俞泽元1, 焦作义,1   
  1. 1. 730030　兰州大学第二医院普外一科
  • 收稿日期:2017-12-24 出版日期:2018-04-01
  • 通信作者: 焦作义
  • 基金资助:
    国家自然科学基金资助项目(31670847); 甘肃省卫生行业科研计划项目(GSWSK2016-03)

A meta-analysis of the relationship between low expression of long non-coding RNA and prognosis of gastric cancer patients

Bo Long1, Keshen Wang1, Yanxian Ren1, Zhijian Ma1, Zeyuan Yu1, Zuoyi Jiao,1   

  1. 1. The First Department of General Surgery, the Second Hospital Affiliated to Lanzhou University, Lanzhou 730030, China
  • Received:2017-12-24 Published:2018-04-01
  • Corresponding author: Zuoyi Jiao
  • About author:
    Corresponding author: Jiao Zuoyi, Email:
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引用本文：

龙勃, 王科深, 任彦先, 马志坚, 俞泽元, 焦作义. 长链非编码RNA低表达与胃癌患者预后关系的Meta分析[J/OL]. 中华普通外科学文献(电子版), 2018, 12(02): 139-144.

Bo Long, Keshen Wang, Yanxian Ren, Zhijian Ma, Zeyuan Yu, Zuoyi Jiao. A meta-analysis of the relationship between low expression of long non-coding RNA and prognosis of gastric cancer patients[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2018, 12(02): 139-144.

目的

对胃癌组织中长链非编码RNA（LncRNA）表达水平与患者临床病理特征关系及预后价值进行系统性评价。

方法

计算机检索中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBMdisc）、万方数据库、重庆维普数据库和英文数据库EMbase、PubMed、The Cochrane Library（2017年4期）、Web of Science，查找建库至2017年4月发表的有关胃癌组织中LncRNA低表达与患者预后的研究。经2名研究人员独立地进行筛选文献、提取数据、质量评价后，采用STATA 12.0软件对数据行Meta分析，Begg's和Egger's漏斗图评价发表偏倚。

结果

共纳入6篇594例胃癌患者LncRNA低表达的研究，组织样本均来自于国内。胃癌患者的LncRNA表达水平与TNM分期（RR=2.06，95% CI =1.73~2.46，P=0.001）、肿瘤浸润深度（RR=2.73，95% CI =2.17~2.43，P=0.001）和区域淋巴结转移（RR=1.63，95% CI =1.37~1.94，P=0.001）相关，而其他临床病理特征与LncRNA表达水平无相关关系，差异无统计学意义。5篇报道胃癌患者总生存期（OS）的研究间存在统计学异质性（I2=68.9%，P=0.012），分析显示与LncRNA高表达组相比，LncRNA低表达组患者的OS较短，总体生存情况较差，差异有统计学意义（HR=0.56，95% CI =0.31~0.99，P=0.046）。3篇报道无疾病进展生存期（DFS）的研究存在统计学异质性（I2=71.0%，P=0.032），分析显示LncRNA高表达组和低表达组间DFS差异无统计学意义（HR=0.57, 95% CI=0.32~1.03，P=0.061）。各项研究对合并OS影响的敏感性分析结果显示合并HR的结果稳定性好，发表偏倚可能性较小（Egger's，P=0.651；Begg's，P=0.806）。

结论

低表达的LncRNA是胃癌预后不良的危险因素，LncRNA的表达水平与胃癌患者的TNM分期、肿瘤的浸润深度和区域淋巴结转移密切相关。

关键词: 胃肿瘤, 长链非编码RNA, 预后, Meta分析
Objective

To systematically evaluate whether the expression level of LncRNA is associated with the clinicopathological features and prognostic value for gastric cancer.

Methods

The Chinese databases including CNKI, CBM, WanFang Databases, VIP Databases, and the English databases including EMbase, PubMed, Cochrane Library (Issue 4, 2017) and Web of Science were systematically searched with the search time end in April 2017. All eligible studies associated with downregulated LncRNA and prognosis in gastric cancer were included. Two researchers independently screened the included studies, extracted data and evaluated the quality. The STATA 12.0 software and Begg's, Egger's funnel maps were used for Meta-analysis and evaluation of publication bias.

Results

A total of six studies about 594 gastric cancer patients which showed the relationship between the low expression level of LncRNA were finally included, and all the tissue samples were from China. The expression level of LncRNA was associated with TNM staging (RR=2.06, 95% CI=1.73-2.46, P=0.001) , the depth of invasion (RR=2.73, 95% CI =2.17-2.43, P=0.001) and the number of lymph node metastases (RR=1.63, 95% CI=1.37-1.94, P=0.001) . There was significant difference in overall survival among the 5 groups (I2=68.9%, P=0.012) , whereas low-regulated LncRNA which showed a shorter overall survival (HR=0.56, 95% CI=0.31-0.99, P=0.046) was statistically significant. There was significant difference in disease free survival among the three studies (I2=71.0%, P=0.032) , while no significant difference between the high-expression group and the low-expression group of LncRNA (HR=0.57, 95% CI=0.32-1.03, P=0.061) . The effects of the 6 studies on the combination of HR and the possibility of publishing bias were small (Egger's, P=0.651; Begg's, P=0.806) .

Conclusions

Low expression of LncRNA is a predictive risk factor for poor prognosis in gastric cancer patients. The expression level of LncRNA is closely related to TNM stage, depth of tumor invasion and regional lymph node metastasis in patients with gastric cancer.

Key words: Stomach neoplasms, Long non-coding RNA, Prognosis, Meta-analysis
图1 PubMed检索策略
图2 文献筛选流程及结果
表1 纳入研究的基本特征
作者，发表年 地区 样本总量 LncRNA名称 方法 截点值 TNM分期 提取方法 结局指标
Fan 2016[12] 中国 138 LINC00261 RT-qPCR 中值 Ⅰ-Ⅳ 文中 DFS
Fei 2016[13] 中国 106 LINC00982 RT-qPCR 中值 Ⅰ-Ⅳ 文中 OS、DFS
Lai 2015[14] 中国 89 ZMAT1 RT-qPCR 中值 Ⅰ-Ⅳ 生存曲线 OS
Sun 2015[15] 中国 96 RP11-119F7.4 RT-qPCR 中值 Ⅰ-Ⅲ 生存曲线 OS、DFS
Sun 2014[16] 中国 72 MEG3 RT-qPCR 中值 Ⅱ-Ⅳ 生存曲线 OS
Zhou 2014[17] 中国 93 LET RT-qPCR 中值 Ⅰ-Ⅳ 文中 OS
表2 纳入研究质量评价结果
作者，发表年 研究对象 减员偏倚 预后因素测量 结局测量 混杂因素的测量和计算 分析方法
Fan 2016[12] 是 是 部分 是 部分 是
Fei 2016[13] 部分 是 是 部分 部分 是
Lai 2015[14] 否 是 是 部分 部分 是
Sun 2015[15] 是 是 部分 是 部分 是
Sun 2014[16] 是 是 是 是 部分 是
Zhou 2014[17] 是 是 是 是 部分 是
表3 纳入研究中LncRNA低表达与临床病理特征的Meta分析结果
临床特征 篇数（n） 异质性检验 效应模型 Meta分析
I2（%）值 P值 RR（95% CI） P值
年龄（≤50岁） 3 57.1 0.097 随机 1.01（0.72~1.43） 0.938
肿瘤大小 5 66.3 0.018 随机 1.13（0.81~1.58） 0.468
肿瘤位置 3 38.2 0.183 固定 1.03（0.88~1.21） 0.690
TNM分期 5 33.1 0.201 固定 2.06（1.73~2.46） 0.001
性别 5 1.1 0.400 固定 0.96（0.83~1.12） 0.642
远处转移 5 79.2 0.001 随机 0.84（0.40~1.75） 0.642
淋巴结站转移 5 89.2 0.001 随机 0.79（0.45~1.40） 0.418
病理分化程度 4 38.2 0.183 固定 1.05（0.82~1.34） 0.691
肿瘤浸润深度 5 0 0.606 固定 2.73（2.17~3.43） 0.001
区域淋巴结转移 3 0 0.715 固定 1.63（1.37~1.94） 0.001
图3 LncRNA低表达与OS关系的Meta分析结果
图4 LncRNA低表达与DFS关系的Meta分析结果
图5 纳入的研究文献敏感性分析图
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