Abstract
BackgroundMounting evidence has shown that long noncoding RNAs (lncRNAs) can play a substantial role in gallbladder cancer (GBC) development as tumor promotors or suppressors, and their abnormal expression is relevant to GBC patient outcomes. We completed this systematic review and meta-analysis to explore the clinical significance and mechanisms of lncRNAs in GBC.MethodsWe conducted a comprehensive literature search and selected eligible records according to the inclusion and exclusion criteria. Hazard ratios (HRs) and odds ratios (ORs) were extracted or calculated to estimate the relationships of high lncRNA expression with GBC patient survival and clinical outcomes.ResultsEighteen studies were identified as eligible for this systematic review and meta-analysis. Heterogeneity among HRs of overall survival (OS) was notably high (I2 = 86.2%, p < 0.001). Subgroup analysis suggested that overexpression of lncRNAs in a group that is upregulated in GBC showed a significant association with poor OS (HR = 2.454, 95% CI 2.004–3.004, I2 = 0%). Conversely, overexpression of lncRNAs in a downregulated group was markedly related to good OS (HR = 0.371, 95% CI 0.267–0.517, I2 = 0%). High expression levels of lncRNA AFAP1-AS1, MALAT1 and ROR were positively correlated with tumor size. Expression of lncRNA LET, LINC00152 and HEGBC exhibited a positive correlation with high T status. LncRNA LINC00152, HEGBC, MALAT1 and ROR showed a marked correlation with positive lymph node metastasis (LNM), while lncRNA GCASPC, MEG3, LET and UCA1 had the opposite effect. High expression levels of lncRNA HEGBC, PAGBC, PVT1 and UCA1 predicted high tumor node metastasis (TNM) stages, while lncRNA LET, GCASPC and MEG3 indicated low TNM stages. We also summarized the mechanisms of lncRNAs in GBC.ConclusionAberrant expression of several lncRNAs was indicative of the prognosis of GBC patients, and lncRNAs showed promise as biomarkers and therapeutic targets for GBC.
Highlights
Mounting evidence has shown that long noncoding RNAs can play a substantial role in gallbladder cancer (GBC) development as tumor promotors or suppressors, and their abnormal expression is relevant to GBC patient outcomes
Selection criteria Studies from the literature search were included based on the following criteria: (1) LncRNA expression was detected in gallbladder cancer tissues; (2) the diagnosis of gallbladder cancer was confirmed by pathology and histology; (3) the relationship between long noncoding RNA (lncRNA) expression and gallbladder cancer patient prognosis was investigated, including survival and clinicopathological parameters; and (4) sufficient data were provided for the hazard ratio (HR) and the 95% confidence interval of survival or the odds ratio (OR) and the 95% CI of clinicopathological parameters
All lncRNA expression levels were detected by quantitative real-time polymerase chain reaction
Summary
Mounting evidence has shown that long noncoding RNAs (lncRNAs) can play a substantial role in gallbladder cancer (GBC) development as tumor promotors or suppressors, and their abnormal expression is relevant to GBC patient outcomes. We completed this systematic review and meta-analysis to explore the clinical significance and mechanisms of lncRNAs in GBC. Gallbladder cancer (GBC) is the most common malignant extrahepatic biliary duct tumor with high malignancy [1]. Statistics show an estimated 12,360 new gallbladder cancer and other biliary cancer cases and 3960 related deaths in the United States in 2019 [2]. When the tumor grows up to a large size do symptoms appear, such as pain, jaundice and fever [3]. Exploring novel biomarkers and therapeutic targets for GBC is a top priority
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