RESUMO
Objective To verify the expressions of genes associated with colorectal cancer with hyperglycemia and evaluate their diagnostic values.Methods Tumor tissues,distal normal intestinal mucosa,and peripheral blood samples were harvested from 109 colorectal cancer patients and peripheral blood samples from 30 diabetes patients and 30 healthy volunteers. The mRNA expressions of glucose regulated protein 78 (GRP78),NADPH oxidase-1 (NOX1),carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5),heat shock protein 60 (HSP60),and histone deacetylase 1(HDAC1) were detected by real-time quantitative polymerase chain reaction. The correlation between the gene expressions and clinicopathological parameters in colorectal cancer patients were analyzed using Pearson's correlation analysis. Diagnostic test accuracy evaluation was used to calculate the sensitivity,specificity,accuracy,predictability,Youden index,and likelihood ratio of serum gene expressions in colorectal cancer patients,and the receiver operating characteristic (ROC) curves were drawn. The area under the ROC curve was calculated to evaluate the diagnostic efficiency of the combined detection of multiple genes.Results The mRNA levels of GRP78 (P=0.001),NOX1 (P=0.022),CEACAM5 (P=0.000),HSP60 (P=0.044),and HDAC1 (P=0.047) were positively correlated with the fasting blood glucose level. The mRNA expressions of NOX1 (P=0.000,P=0.008) and HDAC1 (P=0.000,P=0.037) in tissues and serum were significantly higher in colorectal cancer patients than in patients with normal blood glucose levels. The NOX1 mRNA expression was positively correlated with the diameter of colorectal cancer (P=0.013),and the HDAC1 mRNA expression was significantly correlated with the tumor site (P=0.049),depth of primary tumor invasion (P=0.025),and TNM stage (P=0.042). The areas under the ROC curves of NOX1,CEACAM5,and HDAC1 were 0.931,0.852,and 0.860 respectively (all P=0.000). The specificity,accuracy,and negative predictive value of NOX1,HDAC1 mRNA expression in colorectal cancer patients with hyperglycemia were all above 90%. The diagnostic sensitivity and specificity of the combined detection of NOX1,CEACAM5,and HDAC1 were 98.82% and 99.93%,respectively.Conclusion Combined detection of genes associated with colorectal cancer accompanied by hyperglycemia can improve the diagnostic efficiency of early screening.
Assuntos
Humanos , Biomarcadores Tumorais , Genética , Antígeno Carcinoembrionário , Genética , Estudos de Casos e Controles , Neoplasias Colorretais , Diagnóstico , Genética , Diabetes Mellitus , Genética , Proteínas Ligadas por GPI , Genética , Proteínas de Choque Térmico , Genética , Histona Desacetilase 1 , Genética , Hiperglicemia , Diagnóstico , Genética , NADPH Oxidase 1 , Genética , Curva ROCRESUMO
<p><b>OBJECTIVE</b>To screen the regulatory proteins involved in Nox1 promoter activation in a cell model of inflammation and oxidative stress.</p><p><b>METHODS</b>A cell model of inflammation and oxidative stress was established by stimulating A549 cells with tumor necrosis factor-α (TNF-α). The differential proteins binding to Nox1 promoter were screened by DNA pull-down and the binding proteins were separated by 2D electrophoresis and selected according to the their differential expression levels (with over 1.5-fold changes relative to the control level). The screened proteins were finally identified by MALDI-TOF/TOF-MS.</p><p><b>RESULTS</b>Seven differentially expressed protein spots (all upregulated in the cell model) were obtained, among which GLE1, DDX19A, KRT1 and KRT10 were identified by mass spectrometry.</p><p><b>CONCLUSION</b>GLE1, DDX19A, KRT1 and KRT10 participate in the activation of Nox1 promoter in TNF-α-induced A549 cells, and this result provides new insights into the biological roles of the regulatory proteins of Nox1 promoter in inflammation and oxidative stress.</p>