肝脏激酶B1低表达与肿瘤患者不良预后关系再评价的Meta分析
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杨雪婷, Email: 329707435@qq.com

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Meta-analysis of revaluation of relationship between low expression of liver kinase B1 and poor prognosis in cancer patients 
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    摘要:

    背景与目的:近年来,越来越多的研究报道了肿瘤中低表达的肝脏激酶B1(LKB1)与肿瘤患者不良预后的关系,而且LKB1目前被认为是重要的抑癌基因。但是,有极少的研究报告了相反的结果,有研究显示LKB1除了具有抑癌作用外,还具有促癌的作用。在肝癌发病过程中,癌细胞可能会通过激活LKB1/AMPK途径诱导基因突变,例如Ras突变或Skp2过度表达,从而诱导癌细胞生存。本研究通过Meta分析进一步明确LKB1低表达与肿瘤患者不良预后之间的关系。
    方法:通过相关检索词在Pubmed、Embase以及Cochrane Library数据库中检索文献,按照规定的纳入和排除的标准筛选后,对纳入的文献进行数据提取和质量评估,用Meta分析的方法评价LKB1表达与肿瘤患者预后之间的关系,用亚组分析确定异质性的来源,用敏感性分析测定每个单项研究对整体的影响。
    结果:共有23项研究和4 357例患者被纳入本研究。所有纳入研究的NOS得分在5~8分之间,中位数为6.65分。其中,22项研究报告了总体生存率(OS),结果显示,LKB1低表达与癌症患者不良OS有关(合并HR=1.94,95% CI=1.55~2.43,P<0.001);12项研究报告了无病生存率(DFS)/无进展生存率(PFS)/无复发生存率/(RFS),结果显示,LKB1低表达与癌症患者不良DFS/RFS/PFS有关(合并HR=1.53,95% CI=1.08~2.17,P=0.017)。进一步亚组分析结果显示,风险或保护因素是异质性的主要来源。最后,敏感度分析的结果排除了每个单项研究对整体具有明显影响的可能性。
    结论:尽管有极少的研究报道了LKB1在肿瘤患者中的促癌作用,LKB1表达升高可能促进肿瘤发展,但本研究证实了低表达的LKB1与多种类型肿瘤患者的不良预后密切相关。

    Abstract:

    Background and Aims: In recent years, an increasing number of researches have reported the relationship between the low expression of liver kinase B1 (LKB1) and the poor prognosis in cancer patients. However, a very few studies have reported opposite results, and some studies have shown that in addition to its anti-cancer effect, LKB1 also has a cancer-promoting effect. In the pathogenesis process of liver cancer, cancer cells may obtain genetic changes and induce cancer cell survival by activating the LKB1/AMPK pathway, such as Ras mutation or Skp2 overexpression. This study was conducted to further determine the relationship between low-expressing LKB1 and poor prognosis in cancer patients.  
    Methods: Literature searches were performed in Pubmed, Embase, and Cochrane Library databases by using relevant search terms. After literature screening according to the inclusion and exclusion criteria, data extraction and quality assessment were performed. The the relationship between LKB1 expression and prognosis of cancer patients were evaluated by Meta-analysis, the source of statistical heterogeneity was determined by subgroup analysis, and the influence of each individual study on the overall results was detected by sensitivity analysis.
    Results: A total of 23 studies with 4 357 patients were finally. The NOS scores for all included studies ranged from 5 to 8, with a median score of 6.65. Among the studies, 22 reported the overall survival (OS), and the results showed that low LKB1 expression was associated with the unfavorable prognosis of the cancer patients (pooled HR=1.94, 95% CI=1.55–2.43, P<0.001); 12 studies reported the disease-free survival (DFS)/progression-free survival (PFS)/relapse-free survival (RFS), and the results showed that low LKB1 expression was associated with poor DFS/PFS/RFS of the cancer patients (pooled HR=1.53, 95% CI=1.08–2.17, P=0.017). The results of further subgroup analysis revealed that the risk or protective factors were the main source of heterogeneity. Finally, the results of the sensitivity analysis excluded the influence of each individual study on the overall results.
    Conclusion: Although a very few studies have reported the pro-cancer effect of LKB1 in tumors, and the increased LKB1 expression may promote cancer development, this study confirms that low LKB1 expression is significantly associated with poor prognosis in patients with different types of cancers. 

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廖东旭, 杨冲, 郑波, 杨雪婷.肝脏激酶B1低表达与肿瘤患者不良预后关系再评价的Meta分析[J].中国普通外科杂志,2020,29(2):228-240.
DOI:10.7659/j. issn.1005-6947.2020.02.015

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  • 收稿日期:2019-12-20
  • 最后修改日期:2019-12-20
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  • 在线发布日期: 2020-02-25