NRAGE is a potential diagnostic biomarker of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related deaths worldwide. Early diagnosis of HCC remains a great challenge in clinic. Novel and effective biomarkers are in urgent need in early diagnosis of HCC.Serum levels of neurotrophin-receptor-interacting melanoma antigen-encoding gene homolog (NRAGE) were measured for 107 patients with HCC, 98 patients with benign liver diseases, and 89 healthy controls using quantitative real-time polymerase chain reaction. Receiver operating characteristic curve was applied to evaluate the diagnostic capacity of serum NRAGE in HCC.NRAGE expression was significantly higher in patients with HCC than in controls (all, P < .05). Moreover, its expression was tightly correlated with TNM stage (P = .004). NRAGE could distinguish patients with HCC from healthy controls with the area under the curve (AUC) of 0.874, yielding a sensitivity of 81.3% and a specificity of 78.7%. Additionally, in differentiation between benign liver diseases and HCC, the AUC value of NRAGE was 0.726, with a sensitivity of 63.6% and a specificity of 73.5%. Meanwhile, alpha-fetoprotein also could distinguish patients with HCC from benign liver disease cases, with an AUC of 0.677, a sensitivity of 64.4%, and a specificity of 60.2%.NRAGE could be a potential biomarker for HCC early diagnosis.

<p>Bioinformatics analysis of molecular genetic targets and key pathways for hepatocellular carcinoma</p>

“…Recently, bioinformatics analyses have been used for identifying novel diagnosis markers and therapeutic targets for many cancers 21–23. Zou et al24 identified NRAGE as a novel biomarker for HCC by integrated bioinformatics analysis. Furthermore, in early HCC, the G2/M checkpoint participated in the progression 25.…”

NRAGE Confers Radiation Resistance in 2D and 3D Cell Culture and Poor Outcome in Patients With Esophageal Squamous Cell Carcinoma

“…Initially, NRAGE was reported as a cancer suppressor gene, which promotes cell apoptosis via binding to p75 neurotrophin receptor (P75NTR) (16,17), Che-1 (18), XIAP-TAK1-TAB1 (19), and UNC5H1 (20) and inhibits proliferation (21) and angiogenesis (22). Contradictorily, functions such as pro-apoptotic gene and growth promotion were slowly discovered (12)(13)(14)(23)(24)(25)(26). Kodera et al (25) found that increased NRAGE expression affects the malignant phenotype of hepatocellular carcinoma (HCC) via its interaction with apoptosis antagonizing transcription factor (AATF).…”

“…Kodera et al (25) found that increased NRAGE expression affects the malignant phenotype of hepatocellular carcinoma (HCC) via its interaction with apoptosis antagonizing transcription factor (AATF). Zou et al (24) proved that NRAGE may be a potential biomarker for HCC early diagnosis due to its ability of distinguishing HCC from benign liver disease. Yang et al (26) reported that an aberrant NRAGE expression in both mRNA and protein levels in ESCC tissues was detected and could induce DNA-damaging chemoresistance by regulating homologous recombination repair.…”

NRAGE, a potential biomarker, induces radioresistance in two- and three-dimensional culture and confers poor prognosis in esophageal squamous cell carcinoma

“…Initially, NRAGE was reported as a cancer suppressor gene, which promotes cell apoptosis via binding to P75NTR [13], Che-1 [14], XIAP-TAK1-TAB1 [15], and UNC5H1 [16] and inhibits proliferation [17] and angiogenesis [18]. Contradictorily, functions such as pro-apoptotic gene and growth promotion were slowly discovered [9,11,[19][20][21][22]. Kodera et al [21] found that increased NRAGE expression affects the malignant phenotype of HCC via its interaction with AATF.…”

“…Kodera et al [21] found that increased NRAGE expression affects the malignant phenotype of HCC via its interaction with AATF. Zou et al [20] proved that NRAGE may be a potential biomarker for HCC early diagnosis due to its ability of distinguishing HCC from benign liver disease. Yang et al [22] reported that an aberrant NRAGE expression in both mRNA and protein levels in ESCC tissues was detected and could induce DNA-damaging chemoresistance by regulating homologous recombination repair.…”