Abstract
BackgroundExpression 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.MethodsWe 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.ResultsThree 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 (I2 = 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.ConclusionsMultiple 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-016-0535-1) contains supplementary material, which is available to authorized users.
Highlights
Expression of various long noncoding Ribonucleic acid (RNA) may affect cancer prognosis
We aimed to examine the potential role of all long noncoding RNAs (lncRNAs) ever investigated in the context of cancer survival prediction, as novel predictors of survival in human cancer
Median sample size was 90 (IQR, 82; range, 30–997) and 69/127 datasets contained less than 100 participants (50 of which datasets came from China)
Summary
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. Informative biomarkers based on ncRNAs include microRNAs (miRs) [5] and the larger long non-coding RNAs (lncRNAs). NcRNAs were up to recently disregarded as ‘junk’ and despite constituting the large majority of RNAs being transcribed, their role in normal development and cellular physiology in health and disease is only recently becoming apparent [2, 6, 7]. LncRNAs refer to any ncRNA consisting of more than 200 nucleotides. They are functionally heterogeneous molecules [6, 8], themselves sub-classified into large intergenic non-coding RNAs (lincRNA), transcribed ultraconserved regions (T-UCRs) and many others [2]. Well-studied examples include the lncRNA Xist, which initiates X-chromosome inactivation in female cells by recruiting repressive complexes to the Xchromosome under inactivation [16,17,18] and H19, which has been shown to play a significant role in genomic imprinting [19, 20]
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