lncRNAs as potential molecular biomarkers in the clinicopathology and prognosis of cholangiocarcinoma: a systematic review and meta-analysis

BACKGROUND: Cholangiocarcinoma (CCA) is the second most common fatal primary hepatobiliary malignant carcinoma, characterized by early invasion and extremely poor outcomes. It is therefore necessary to identify a novel biomarker to better diagnose CAA and predict its prognosis. Recently, emerging evidence has revealed that some lncRNAs play an important role in the tumorigenesis and progression of CAA. In order to support this search for novel diagnostic and prognostic biomarkers for CAA, we conducted a meta-analysis to analyze the published association between lncRNA expression and its clinical value in CAA. METHODS: Eligible studies were pooled and analyzed according to our inclusion and exclusion criteria after a comprehensive literature search. Stata 14.0 software was used to analyze the data from relevant studies and to construct a forest plot. Different effect sizes were selected for the meta-analysis. RESULTS: In total, 24 publications were included in this meta-analysis. After review of their full-text, 16 articles studied the association between lncRNAs and clinicopathological characteristics, 2 discussing diagnosis and 16 discussing prognosis. Our results showed that overexpression of CCAT1 was significantly correlated with tumor stage (I + II vs III + IV) (OR, 4.99; 95% CI 2.77–8.99; P<0.001) and lymph node metastasis in CCA (OR, 4.75; 95% CI 2.65–8.52; P<0.001). Furthermore, elevated CCAT lncRNA family expression predicted a shorter overall survival (HR, 2.09; 95% CI 1.17–3.00; P<0.001), especially CCAT2. Upregulation of CCAT2 was also obviously associated with tumor stage in CCA (OR, 5.29; 95% CI 2.64–10.58; P=0.001). CONCLUSION: This is the first meta-analysis to assess the relationship between expression of lncRNAs and the clinical values of patients with CCA. lncRNAs can function as potential molecular biomarkers of the clinicopathology and prognosis of CCA.