Expression of the Wnt ligands gene family and its relationship to prognosis in hepatocellular carcinoma

Abstract

Background: The Wnt gene family members are known to participate regulating various normal and pathological processes including tumorigenesis. However, the association between Wnt ligands gene family and prognosis in hepatocellular carcinoma has not been systematically studied. Therefore, we evaluated the role of Wnt ligands gene family in hepatocellular carcinoma using publicly available data from The Cancer Genome Atlas (TCGA). Methods: Clinical information and RNA-Seq mRNA expression data were derived from TCGA hepatocellular carcinoma cohort. Differences in overall survival (OS) and disease-free survival (DFS) between increased and decreased expression groups (defined by X-tile analyses) of Wnt ligands gene family were compared using Kaplan-Meier method and Cox regression model, with p-values calculated via log-rank test. Gene Set Enrichment Analysis (GSEA) was performed. Results: Multivariate analysis adjusted for patient age, sex, BMI, tumor grade, and TMN stage revealed that Wnt1, Wnt3 and Wnt5B expressions were independent prognostic factors for OS and DFS (OS: HR = 0.58, P = 0.006; HR = 0.65, P = 0.03; HR = 0.56, P = 0.023, respectively; DFS: HR = 0.52, P < 0.001; HR = 1.93, P = 0.003; HR = 0.59, P = 0.011, respectively). Furthermore, expression of Wnt1 and Wnt5B was significantly associated with TMN stage (P = 0.02 and P = 0.03 for OS; P = 0.02 and P = 0.02 for DFS). GSEA showed that nucleotide excision repair was differentially enriched in Wnt1 low expression phenotype and aminoacyl trna biosynthesis and basal transcription factors were differentially enriched in Wnt5B low expression phenotype. Conclusions: Our results identified associations of several Wnt ligands with prognosis of HCC patients, indicating that these genes could serve as prognostic biomarkers of HCC.