Diagnostic and prognostic value of WNT family gene expression in hepatitis B virus-related hepatocellular carcinoma

The aim of the present study was to investigate the diagnostic and prognostic value of Wingless-type MMTV integration site (WNT) gene family expression in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The clinical data of the patients and gene expression levels were downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Receiver operating characteristic curve analysis was used to investigate the diagnostic value of WNT genes. Cox proportional hazard regression analysis and Kaplan-Meier survival analysis were performed to evaluate the association of WNT gene expression level with overall survival (OS) and recurrence-free survival (RFS). A nomogram was constructed for the prediction of prognosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Diagnostic receiver operating characteristic curve analysis suggested that WNT2 had a high diagnostic value, with an area under the curve (AUC) of >0.800 (P<0.0001, AUC=0.810, 95% CI: 0.767–0.852). Survival analysis indicated that the expression level of WNT1 was significantly associated with OS and RFS (adjusted P=0.033, adjusted HR=0.607, 95% CI: 0.384–0.960; and adjusted P=0.007, adjusted HR=0.592, 95% CI: 0.404–0.868, respectively). In the TCGA validation cohort, we also observed that WNT2 was significantly differentially expressed between HCC tissues and adjacent non-tumor tissues, and WNT1 was associated with both the OS and RFS of HCC. Therefore, through the GSE14520 HBV-related HCC cohort we concluded that WNT2 may serve as a diagnostic biomarker and WNT1 may serve as a prognostic biomarker. These results may also be extended to TCGA HCC verification cohort.