High Expression of Neuro-Oncological Ventral Antigen 1 Correlates with Poor Prognosis in Hepatocellular Carcinoma

Yi-An Zhang,Tao-Tao Liu,Ji-Min Zhu,Jie Yin,Xi-Zhong Shen,Wen-Qing Tang,Yan-Mei Guo,Xin-Yuan Guan

doi:10.1371/journal.pone.0090955

Abstract

Neuro-oncological ventral antigen 1 (Nova1) is a neuron-specific RNA-binding protein in human paraneoplastic opsoclonus-myoclonus ataxia accompanying with malignant tumors, but its role in hepatocellular carcinoma (HCC) remains elusive. In this study, we found that overexpressed intratumoral Nova1 was associated with poor survival rate and increased recurrence rate of HCC, especially early recurrence, and was an independent prognostic factor for overall survival rate and tumor recurrence. HCC cell lines over-expressing Nova1 exhibited greater potentials in cell proliferation, invasion and migration, while knockdown of Nova1 had the opposite effects. All these findings indicate that Nova1 may act as a prognostic marker for poor outcome and high recurrence in HCC.

Highlights

Hepatocellular carcinoma (HCC) represents the third cause of cancer-related death worldwide [1]
Intratumoral Neuro-oncological ventral antigen 1 (Nova1) was an unfavorable predictor for Overall survival rate (OS) and Time to recurrence rate (TTR) (HR = 2.210 and 2.543, respectively, P, 0.01; Table 2)
Nova1 was the first identified RNA binding protein in human paraneoplastic opsoclonus-myoclonus ataxia (POMA) [4], and previously regarded as a specific neuron’s protein [17]. Studies recognized it as an onconeural antigen in the antisera of patients with POMA, a motor disorder of brainstem, cerebella, and spinal motor neurons associated with cancer

Summary

Introduction

Hepatocellular carcinoma (HCC) represents the third cause of cancer-related death worldwide [1]. Surgical resection improves survival rate of early-stage HCC patients, the high recurrence rate still exists. Neuro-oncological ventral antigen 1 (Nova1) was first identified as a neuron-specific RNA binding protein in paraneoplastic opsoclonus-myoclonus ataxia (POMA), which is associated with breast cancer, fallopian cancer and small cell lung cancer [4,5]. The aberrant expression of Nova in tumor cells interferes the RNA-binding activity and triggers host immune response, leading to the development of POMA [6]. Autoantibodies against Nova were found in the serum and/or cerebrospinal fluid of patients before the cancer becomes symptomatic, which implies that these antibodies may have utility for early detection of these disorders [7]. Nova expression in HCC has not yet been observed

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