Abstract

Neural precursor cell expressed, developmentally downregulated 9 (NEDD9) plays an integral role in natural and pathological cell biology. Overexpression of NEDD9 protein has been correlated with poor prognosis in various types of cancer. However, few available data address the precise function of the NEDD9 gene in hepatocellular carcinoma (HCC). In the present study, we investigated NEDD9 expression in 40 primary human HCC tissues compared with matched adjacent non-tumor hepatic tissues using RT-qPCR and western blot analysis. Immunohistochemistry was performed to analyze the correlations between NEDD9 expression and clinicopathological factors. Statistical analyses were applied to derive prognostic values of NEDD9 in HCC. The results showed that the NEDD9 mRNA and protein expression levels in HCC tissues were significantly higher than those in matched adjacent non-tumor hepatic tissues. High NEDD9 expression was correlated with larger tumor size, advanced tumor grade, metastasis, intrahepatic venous invasion and high UICC TNM stages in HCC patients. Patients with high NEDD9 expression levels exhibited poorer recurrence-free and overall survival than those with a low NEDD9 expression. Additionally, NEDD9 expression status was an independent prognostic factor for survival. This correlation remained significant in patients with early-stage HCC or with normal serum AFP levels. The results of this study suggest that NEDD9 may be a valuable prognostic biomarker for HCC, including early-stage and AFP-normal patients.

Highlights

  • Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor due to increases in the rates of viral hepatitis and adiposis hepatica

  • Analysis of NEDD9 mRNA expression. mRNA expression levels of NEDD9 were evaluated in 40 pairs of resected specimens from patients with HCC using reverse-transcription quantitative polymerase chain reaction (RT-Quantitative PCR (qPCR))

  • The results indicated that the relative expression levels of NEDD9 mRNA in HCC tissues were significantly higher than those in adjacent non-tumor hepatic tissues (ANHT) (4.38±0.65 vs. 3.21±0.71, P

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor due to increases in the rates of viral hepatitis and adiposis hepatica. HCC is the third leading cause of cancer mortality worldwide [1,2]. Each year, ~650,000 HCC cases are reported globally, and according to statistics, China alone accounts for 55% of HCC cases worldwide [3,4]. Hepatic resection is the gold standard therapy for HCC [5]. The survival of patients with HCC has been greatly improved owing to advances in surgical improvements and perioperative management, long-term survival after surgical resection remains low due to the high rates of recurrence and metastasis [6,7]. The recurrence and metastasis of HCC are multistep processes that involve complex biological and pathological events [8,9]. Several molecular pathways and abnormal genetic changes are involved [10]

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