WDR62在肝细胞肝癌中的表达及预后价值OA

Objective To investigate the expression pattern of WD repeat-containing protein 62(WDR62)in hepatocellular carcinoma(HCC),its association with clinicopathological features and prognosis,and to construct a prognostic nomogram model for overall survival(OS)based on WDR62.Methods RNA sequencing data and clinical information for HCC were obtained from The Cancer Genome Atlas Liver Hepatocellular Carcinoma cohort(TCGA-LIHC).WDR62 messenger RNA(mRNA)expression was compared between tumor and adjacent non-tumor liver tissues.Its diagnostic value was assessed using receiver operating characteristic(ROC)curves.Patients were divided into high-and low-expression groups according to the median WDR62 expression level.Associations between WDR62 expression and clinicopathological variables,as well as survival outcomes including OS,disease-specific survival(DSS)and progression-free survival(PFS)were analyzed.Univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent prognostic factors for OS.Subsequently,a prognostic nomogram was constructed.Harrell's concordance index(C-index),calibration curves and decision curve analysis(DC A)were used to assess model performance.In addition,paired HCC and adjacent liver tissues from surgical specimens in our hospital were collected from the Second Affiliated Hospital of Kunming Medical University,and WDR62 protein expression was examined by immunohistochemistry(IHC).Results A total of 424 HCC cases and 50 adjacent/normal liver tissues samples from TCGA-LIHC were included.WDR62 mRNA expression was significantly higher in HCC tissues than in adjacent tissues(P＜0.001),with an area under the ROC curve(AUC)of 0.964 for distinguishing HCC from adjacent/normal tissues.The high WDR62 expression group exhibited higher proportions of patients with pathological stage Ⅲ-Ⅳ,histologic grade G3-G4,alpha-fetoprotein(AFP)＞400 ng/mL and the presence of tumor status,and a higher incidence of OS events(P＜0.05).Kaplan-Meier curves showed significantly poorer OS,DSS and PFS in the high-expression group(OS:P=0.004).Multivariate Cox analysis identified pathological T3～T4 stage,presence of tumor status and high WDR62 expression as independent risk factors for OS;high WDR62 expression had a hazard ratio(HR)of 1.656(95％confidence interval[CI]:1.028～2.667,P=0.038).The nomogram model achieved a Harrell's C-index of 0.629(95％CI:0.576～0.680).Calibration curves for 1-,3-and 5-year OS showed good agreement,and DCA indicated that the model provided higher net benefit within a threshold probability range of approximately 0.05～0.20.In the hospital IHC cohort,WDR62 protein expression was also significantly higher in HCC tissues than in paired adjacent tissues(P＜0.05).Conclusion WDR62 is up-regulated in HCC and is closely associated with tumor progression and poor prognosis.The OS prognostic nomogram constructed based on WDR62 and clinicopathological variables shows acceptable predictive capability within the TCGA-LIHC cohort.