Transcriptome Analysis Identifies Oxidative Stress Injury Biomarkers for Diabetic Nephropathy

摘要

? 2022 Instituto Mexicano del Seguro Social (IMSS)Background: The early diagnosis of diabetic nephropathy (DN) is essential for improving the prognosis and effectively manage patients affected with this disease. The standard biomarkers, including albuminuria and glomerular filtration rate, are not very precise. New molecular biomarkers are needed to more accurately identify DN and better predict disease progression. Characteristic DN biomarkers can be identified using transcriptomic analysis. Aim of the Study: To evaluate the transcriptomic profile of controls (CTRLs, n = 15), patients with prediabetes (PREDM, n = 15), patients with type-2 diabetes mellitus (DM2, n = 15), and patients with DN (n = 15) by microarray analysis to find new biomarkers. RT-PCR was then used to confirm gene biomarkers specific for DN. Materials and Methods: Blood samples were used to isolate RNA for microarray expression analysis. 26,803 unique gene sequences and 30,606 LncRNA sequences were evaluated-Selected gene biomarkers for DN were validated using qPCR assays. Sensitivity, specificity, and area under the curve (AUC) were calculated as measures of diagnostic accuracy. Results: The DN transcriptome was composed of 300 induced genes, compared to CTRLs, PREDM, and DM-2 groups. RT-qPCR assays validated that METLL22, PFKL, CCNB1 and CASP2 genes were induced in the DN group compared to CTRLs, PREDM, and DM-2 groups. The ROC analysis for these four genes showed 0.9719, 0.8853, 0.8533 and 0.7748 AUC values, respectively. Conclusion: Among induced genes in the DN group, we found that CASP2, PFKL and CCNB1 may potentially be used as biomarkers to diagnose DN. Of these, METLL22 had the highest AUC score, at 0.9719.