An integrated mRNA–lncRNA signature for overall survival prediction in cholangiocarcinoma

Abstract

The combination of mRNA and lncRNA profiles for establishing an integrated mRNA–lncRNA prognostic signature has remained unexplored in cholangiocarcinoma (CCA) patients. We utilized a training dataset of 36 samples from The Cancer Genome Atlas dataset and a validation cohort (GSE107943) of 30 samples from Gene Expression Omnibus. Two mRNAs (CFHR3 and PIWIL4) and 2 lncRNAs (AC007285.1 and AC134682.1) were identified to construct the integrated signature through a univariate Cox regression (P-value = 1.35E−02) and a multivariable Cox analysis (P-value = 3.07E−02). Kaplan–Meier curve showed that patients with low risk scores had notably prolonged overall survival than those with high risk scores (P-value = 4.61E−03). Subsequently, the signature was validated in GSE107943 cohort with an area under the curve of 0.750 at 1-year and 0.729 at 3-year. The signature was not only independent from diverse clinical features (P-value = 3.07E−02), but also surpassed other clinical characteristics as prognostic biomarkers with area under the curve of 0.781 at 3-year. Moreover, the weighted gene co-expression network analysis and gene enrichment analyses found that the integrated signature were associated with metabolic-related biological process and lipid metabolism pathway, which has been implicated in the pathogenesis of CCA. Taken together, we developed an integrated mRNA–lncRNA signature that had an independent prognostic value in the risk stratification of patients with CCA.