Overexpression of NDRG1 is an indicator of poor prognosis in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma is a highly lethal cancer that typically has poor prognosis. Prognostic markers can help in its clinical management and in understanding the biology of poor prognosis. Through an earlier gene expression study, we identified N-Myc downregulated gene 1 (NDRG1) to be significantly highly expressed in hepatocellular carcinoma compared to nontumor liver. As NDRG1 is a differentiation-related gene with putative metastasis suppressor activity, we investigated the clinical significance of its overexpression. Quantitative realtime polymerase chain reaction using an independent set of patient samples confirmed the significant overexpression of NDRG1 in hepatocellular carcinoma compared to nontumor liver samples (Po0.001). Additionally, high levels of NDRG1 transcript correlated with shorter overall survival (Po0.001), late tumor stage (P ¼ 0.001), vascular invasion (P ¼ 0.003), large tumor size (P ¼ 0.011), and high Edmondson-Steiner histological grade (P ¼ 0.005). Using immunohistochemistry, NDRG1 protein was found to be significantly overexpressed in hepatocellular carcinoma samples compared to nontumor liver or cirrhotic and benign liver lesions (Po0.001). Among the hepatocellular carcinoma samples, those which are moderately and poorly differentiated express higher levels of NDRG1 protein than those which are well-differentiated (Po0.005). Additionally, hepatocellular carcinomas with vascular invasion also express elevated levels of NDRG1 protein compared to those without vascular invasion (significant at Po0.005). Our results suggest NDRG1 to be a likely tumor marker for hepatocellular carcinoma, the overexpression of which is correlated with tumor differentiation, vascular invasion, and overall survival. Its significantly elevated expression in hepatocellular carcinoma could be a useful indicator of tumor aggressiveness and therefore patient prognosis. Modern Pathology (2007) 20, 76-83.

NDRG1 prognosticates the natural course of disease in WHO grade II glioma

“…In line with these preclinical findings NDRG1 expression is associated with a favorable prognosis in patients with breast, colon or pancreatic cancer [28,30,31], but associated with more aggressive disease in cervical or liver cancer [32,33]. In these studies, effects on tumor growth and therapy-modifying properties of NDRG1 are not separable.…”

Metastasis-related Plasma Membrane Proteins of Human Breast Cancer Cells Identified by Comparative Quantitative Mass Spectrometry

“…The function of this protein remains unclear, and some controversy regarding its role in cancer exists. Some studies suggest NDRG1 involvement in metastatic suppression, whereas others show higher expression of this protein, likely related to metastasis (51)(52)(53)(54)(55). The difference in subcellular localization of NDRG1 may be important for its function, and we therefore remain open to the concept that it plays some role in the development of metastases.…”

MiR-29a Assists in Preventing the Activation of Human Stellate Cells and Promotes Recovery From Liver Fibrosis in Mice

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