Serghiou Stylianos, Kyriakopoulou Aikaterini, Ioannidis John P A
St. John's Hospital, Livingston, EH54 6PP, UK.
College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK.
Mol Cancer. 2016 Jun 28;15(1):50. doi: 10.1186/s12943-016-0535-1.
BACKGROUND: Expression of various long noncoding RNAs (lncRNAs) may affect cancer prognosis. Here, we aim to gather and examine all evidence on the potential role of lncRNAs as novel predictors of survival in human cancer. METHODS: We systematically searched through PubMed, to identify all published studies reporting on the association between any individual lncRNA or group of lncRNAs with prognosis in human cancer (death or other clinical outcomes). Where appropriate, we then performed quantitative synthesis of those results using meta-analytic methods to identify the true effect size of lncRNAs on cancer prognosis. The reliability of those results was then examined using measures of heterogeneity and testing for selective reporting biases. RESULTS: Three hundred ninety-two studies were screened to eventually identify 111 eligible studies on 127 datasets. In total, these represented 16,754 independent participants pertaining to 53 individual and 6 grouped lncRNAs within a total of 19 cancer sites. Overall, 83 % of the studies we identified addressed overall survival and 32 % of the studies addressed recurrence-free survival. For overall survival, 96 % (88/92) of studies identified a statistically significant association of lncRNA expression to prognosis. Meta-analysis of 6 out of 7 lncRNAs for which three or more studies were available, identified statistically significant associations with overall survival. The lncRNA HOTAIR was by far the most broadly studied lncRNA (n = 29; of 111 studies) and featured a summary hazard ratio (HR) of 2.22 (95 % confidence interval (CI), 1.86-2.65) with modest heterogeneity (I(2) = 49 %; 95 % CI, 14-79 %). Prominent excess significance was demonstrated across all meta-analyses (p-value = 0.0003), raising the possibility of substantial selective reporting biases. CONCLUSIONS: Multiple lncRNAs have been shown to be strongly associated with prognosis in diverse cancers, but substantial bias cannot be excluded in this field and larger studies are needed to understand whether these prognostic information may eventually be useful.
背景：多种长链非编码RNA（lncRNA）的表达可能影响癌症预后。在此，我们旨在收集并审视关于lncRNA作为人类癌症生存新预测指标潜在作用的所有证据。 方法：我们系统检索了PubMed，以识别所有已发表的报告任何单个lncRNA或lncRNA组与人类癌症预后（死亡或其他临床结局）之间关联的研究。在适当情况下，我们随后使用荟萃分析方法对这些结果进行定量综合，以确定lncRNA对癌症预后的真实效应大小。然后使用异质性测量和选择性报告偏倚检验来检查这些结果的可靠性。 结果：共筛选了392项研究，最终确定了127个数据集的111项合格研究。这些研究总共涉及19个癌症部位的16754名独立参与者，涉及53个单个lncRNA和6个lncRNA组。总体而言，我们确定的研究中83%涉及总生存期，32%涉及无复发生存期。对于总生存期，96%（88/92）的研究确定lncRNA表达与预后存在统计学显著关联。对7个lncRNA中的6个进行荟萃分析（每个lncRNA有三项或更多研究），确定与总生存期存在统计学显著关联。lncRNA HOTAIR是迄今为止研究最广泛的lncRNA（在111项研究中有29项），其汇总风险比（HR）为2.22（95%置信区间（CI），1.86 - 2.65），异质性适中（I(2)=49%；95%CI，14 - 79%）。在所有荟萃分析中均显示出显著的过度显著性（p值 = 0.0003），增加了存在大量选择性报告偏倚的可能性。 结论：多种lncRNA已被证明与多种癌症的预后密切相关，但该领域不能排除存在大量偏倚，需要更大规模的研究来了解这些预后信息最终是否有用。
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