Combined aberrant expression of N-Myc downstream-regulated gene 2 and CD24 is associated with disease-free survival and overall survival in patients with hepatocellular carcinoma

BACKGROUND: N-Myc downstream-regulated gene 2 (NDRG2), as a tumor suppressor, has been demonstrated to inhibit tumor invasion and migration of hepatocellular carcinoma (HCC) by reducing the expression of CD24, which has been identified as a prognostic factor for HCC patients. However, the clinical significance of combined NDRG2 and CD24 expression in HCC remains unclear. Thus, the aim of the current study was to investigate the relationship of NDRG2 and CD24 expression with clinicopathological parameters and patients’ survival. METHODS: Immunohistochemistry was performed to detect the expression and subcellular localizations of NDRG2 and CD24 proteins in 130 pairs of HCC and adjacent nonneoplastic liver tissues. RESULTS: NDRG2 protein was strongly expressed in the cytoplasm and plasma membrane of hepatocytes in adjacent nonneoplastic liver tissues, whereas its immunostaining was weak or negative in HCC tissues. In contrast, CD24 protein exhibited the cytoplasm immunostaining in tumor cells of HCC tissues but showed negative expression in adjacent nonneoplastic liver tissues. The statistical analysis also showed that the expression levels of NDRG2 and CD24 proteins in HCC tissues were respectively lower and higher than those in adjacent nonneoplastic liver tissues significantly (both P < 0.001). In addition, there was an inverse correlation between NDRG2 expression and CD24 expression in HCC tissues (P = 0.02). Moreover, combined NDRG2 downregulation and CD24 upregulation (NDRG2-low/CD24-high) more frequently occurred in HCC tissues with high serum AFP (P = 0.03), advanced tumor stage (P = 0.001) and high tumor grade (P = 0.02). Furthermore, HCC patients with NDRG2-low/CD24-high expression showed shortest 5-year disease-free survival and 5-year overall survival (both P < 0.001) of four groups (NDRG2-low/CD24-high, NDRG2-low/CD24-low, NDRG2-high/CD24-high, NDRG2-high/CD24-low). Of note, the multivariate survival analysis showed that the combined aberrant expression of NDRG2 and CD24 proteins was an independent prognostic factor for both 5-year disease-free survival and 5-year overall survival (both P = 0.01) in HCC. CONCLUSIONS: These findings suggest that the downregulation of NDRG2 combined with the upregulation of CD24 may play a synergistic role in the occurrence and progression of HCC. A combined detection of NDRG2/CD24 expression may benefit us in determining the prognosis in patients with HCC. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_209