Neuraminidase 1 (NEU1) promotes proliferation and migration as a diagnostic and prognostic biomarker of hepatocellular carcinoma

Oncotarget. 2016 Oct 4;7(40):64957-64966. doi: 10.18632/oncotarget.11778.

Abstract

Hepatocellular carcinoma (HCC) is among the most malignant cancers worldwide, lacking biomarkers for subtyping and the reliable prognostication. Herein, we report a novel biomarker, NEU1 (neuraminidase 1), is up-regulated in most samples of HCC. The diagnostic value of NEU1 was evaluated by ROC, and the AUC (area under curve) reached 0.87 and 0.96 in two independent datasets, respectively. The survival differences of HCC patients with high or low expression of NEU1 were statistically significant, and a significant correlation between NEU1 expression and clinical information including stage, differentiation, AFP and embolus were observed. NEU1 expression, at both the mRNA and protein levels, were also higher in the portal vein tumor thrombus than tumor tissues. We also measured the proliferation and migration ability of two HCC cell lines following NEU1 interference and over-expression. Migration and proliferation rate were increased in NEU1 high expression groups. Moreover, gene expression studies identified pathways significantly associated with NEU1 expression. Among them, all the genes involved in spliceosomepathway were up regulated in NEU1-high group. In summary, our work identified NEU1 as a novel biomarker for both diagnosis and prognosis in HCC, and one of the most altered pathway of NEU1 is spliceosome.

Keywords: hepatocellular carcinoma; migration; neuraminidase 1; prognosis; proliferation.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Neoplasm Staging
  • Neuraminidase / genetics
  • Neuraminidase / metabolism*
  • Predictive Value of Tests
  • Prognosis
  • RNA, Small Interfering / genetics
  • Survival Analysis
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • RNA, Small Interfering
  • NEU1 protein, human
  • Neuraminidase