Abstract
BackgroundThe 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).MethodsClinical 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.ResultsMultivariate 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.ConclusionsOur results identified associations of several Wnt ligands with prognosis of HCC patients, indicating that these genes could serve as prognostic biomarkers of HCC.
Highlights
The Wnt gene family members are known to participate regulating various normal and pathologi‐ cal processes including tumorigenesis
Basic patient characteristics Clinical information and Wnt ligands mRNA expression levels of 360 patients were obtained from The Cancer Genome Atlas (TCGA)
TNM stage was significantly associated with the overall survival (OS) and disease-free survival (DFS) (P < 0.001), but not sex, age, body mass index (BMI), or race
Summary
The Wnt gene family members are known to participate regulating various normal and pathologi‐ cal processes including tumorigenesis. The association between Wnt ligands gene family and prognosis in hepatocellular carcinoma has not been systematically studied. We evaluated the role of Wnt ligands gene family in hepatocellular carcinoma using publicly available data from The Cancer Genome Atlas (TCGA). Hepatocellular carcinoma (HCC), as the most common pathological type, accounts for approximately 90% of primary liver cancers [2]. Numerous studies have reported that aberrant activation of Wnt signaling may contribute to the pathology of various types of cancer, including colon cancer [6], gastric cancer [7], HCC [8]. A comprehensive analysis of the association between the expression of Wnt ligands and clinicopathologic features of hepatocellular carcinoma (HCC) is lacking. To gain further insight into the biological pathways involved in HCC pathogenesis related Wnt regulatory network, GSEA was performed
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