ABSTRACT
N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan-Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan-Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.
Subject(s)
Carcinoma, Hepatocellular/diagnosis , Gene Expression Regulation, Neoplastic , Liver Neoplasms/diagnosis , Nerve Tissue Proteins/genetics , Up-Regulation , Carcinoma, Hepatocellular/genetics , Female , Humans , Intracellular Signaling Peptides and Proteins , Kaplan-Meier Estimate , Liver Neoplasms/genetics , Male , Middle Aged , Nerve Tissue Proteins/analysis , PrognosisABSTRACT
BACKGROUND Sperm-associated antigen 5 (SPAG5), a gene that encodes a mitotic spindle-associated protein, is closely related to tumor development and is involved in cell migration and proliferation. The objective of this research was to explore the clinical significance of SPAG5 expression in hepatocellular carcinoma (HCC) and the relationship between SPAG5 expression and HCC prognosis. MATERIAL AND METHODS Twenty pairs of fresh-frozen HCC samples and samples from 95 HCC patients in a tissue microarray were subjected to quantitative real-time reverse-transcription (qRT)-PCR and immunohistochemistry (IHC), respectively, to investigate the relationship between the expression of SPAG5 and the clinicopathological features of HCC patients. RESULTS PCR data showed that the messenger RNA (mRNA) expression level of SPAG5 in HCC tissue specimens was higher than that in adjacent non-tumor tissue specimens (p<0.05). IHC analyses demonstrated that SPAG5 expression was significantly correlated with tumor grade (p=0.003), tumor number (p=0.009), vascular invasion (p=0.001), and TNM stage (p=0.001). Survival analysis and Kaplan-Meier curves showed that SPAG5 expression is an independent prognostic indicator for disease-free survival (p=0.017) and overall survival (p=0.016) in HCC patients. CONCLUSIONS Our results indicate that SPAG5 expression may be considered as an oncogenic biomarker and a novel predictor for HCC prognosis.
Subject(s)
Carcinoma, Hepatocellular/genetics , Cell Cycle Proteins/genetics , Liver Neoplasms/genetics , Adult , Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/metabolism , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cell Movement/genetics , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Liver Neoplasms/metabolism , Male , Middle Aged , Neoplasm Staging , Prognosis , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Up-RegulationABSTRACT
BACKGROUND: The incidence of hepatocellular carcinoma (HCC) has increased over the past decades in China. Current screening methods of HCC such as detection of α-fetoprotein (AFP) combined with liver ultrasonography remain unsatisfactory. Many HCC patients have already missed the optimal treatment period when diagnosed. Our study aimed to evaluate the value of Glypican 3 (GPC3) and Golgi protein 73 (GP73) in the detection of HCC. METHODS: Thirty-nine patients with HCC and 31 patients with liver cirrhosis were enrolled. The level of serum GPC3 and GP73 were determined by ELISA. The expression of GPC3 mRNA and GP73 mRNA in peripheral blood mononuclear cell (PBMC) and liver tissues were also measured with qRT-PCR. Then, receiving operating characteristic (ROC) curves were plotted to detect the sensitivity and specificity of serum GPC3 and GP73 in the diagnosis of HCC. RESULTS: The levels of serum GPC3 and GP73 in the HCC group were significantly higher than in the cirrhosis group (p < 0.0001). Patients with GPC3 > 9.3 µg/L and GP73 > 77.68 ng/mL had a risk of HCC of 92.31%. The HCC diagnosis ROC curve analysis indicated that when setting the GPC3 cutoff value > 9.3 µg/L, AUC = 0.956. The sensitivity and specificity of GPC3 were 89.74% and 96.77%, respectively, with a positive predictive value of 97.2%, negative predictive value of 88.2%, + LR of 27.82 and - LR of 0.11. When setting GP73 cutoff value > 77.68 ng/mL, AUC = 0.937. The sensitivity and specificity of GP73 were 92.31% and 83.87%, respectively, with positive predictive value of 87.8%, negative predictive value of 89.7%, + LR of 5.72 and - LR of 0.092. No significant difference (p > 0.05) was found between GPC3 and GP73 AUC in ROC curves, indicating that these two biomarkers were equivalent in the prediction of HCC. CONCLUSIONS: The expression of serum GPC3 and GP73 was significantly higher in the HCC patients compared with the cirrhosis patients. GPC3 and GP73 might be effective non-invasive diagnostic indicators of HCC.
