Decreased expression of ZWINT is associated with poor prognosis in patients with HCC after surgery

Abstract

Background: ZW10 interactor was recently reported to correlate with human cancers. However, the prognostic value of ZW10 interactor in hepatocellular carcinoma was not reported. Methods: The expression level of ZW10 interactor was evaluated by Western blot and immunohistochemistry using tissue microarray. In the present study, we used 5 pairs of hepatocellular carcinoma and peritumoral frozen tissues for Western blot, and 70 paired paraffin-embedded hepatocellular carcinoma and peritumoral tissues as expression pattern cohort (cohort 1), and 280 paraffin-embedded hepatocellular carcinoma tissues were used as prognostic cohort (cohort 2). The integral optic density representing the expression level of ZW10 interactor in each tissue sample, was calculated using Image-Pro Plus. The integral optic density was added to the X-tile software for calculating the outcome-based cut point. Kaplan-Meier and Cox regression were used to evaluate the prognostic values. Results: The expression level ZW10 interactor was decreased in hepatocellular carcinoma tissues in 85.7% (60/70) of the cases compared to the corresponding peritumoral tissues evaluated by immunohistochemistry. Similar result was obtained by Western blot analysis using frozen tissue. Expression of ZW10 interactor was closely correlated with age (P = .0001) and liver cirrhosis in cohort 1 and tumor node metastasis (P = .018), tumor size (P = .005), and vascular invasion (P = .022) in cohort 2 based on w2 analyses. Survival analyses indicated that patients with hepatocellular carcinoma having low ZW10 interactor expression had a shorter overall survival time and time to recurrence compared to cases with high ZW10 interactor expression in the prognostic cohort (P < .0001 for both overall survival and time to recurrence ). Univariate and multivariate Cox analyses indicated that ZW10 interactor was an independent prognostic factor for overall survival (P = .033). Conclusions: The present study clearly showed that ZW10 interactor was frequently decreased in hepatocellular carcinoma compared to nontumoral liver tissues, and ZW10 interactor could serve as a potential prognostic marker in patients with hepatocellular carcinoma after surgery.