Correlation Analysis Of Serum FOXO3 Level And Renal Function In Patients With Chronic Kidney Disease Stages 3-5

Objective:To investigate the level of serum FOXO3 in patients with chronic kidney disease stages 3-5(CKD3-5)and to explore its correlation with renal function.Methods:We extracted differentially expressed genes(DEGs)from dataset GSE37171 in the GEO database.GO and KEGG enrichment analyses were performed for up-regulated and down-regulated DEGs to construct PPI network analysis and screen out key genes.Based on the inclusion and exclusion criteria,the clinical data of a total of 89 patients with CKD stages 3-5 in our hospital from October 2020 to October 2021 were collected,including32 cases with CKD stage 3,28 subjects with CKD stage 4 and 29 subjects with CKD stage 5.Thirty subjects were included as normal controls in the same period of physical examination of healthy individuals.We collected general information,such as age,sex,body mass index(BMI)and primary disease.Hemoglobin(Hb),albumin(ALB),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),urea nitrogen(BUN),creatinine(Scr),uric acid(UA),cystatin C(Cys-C),calcium(Ca),phosphorus(P)and other indicators were collected from CKD3-5 patients.Serum FOXO3 levels were measured by enzyme-linked immunosorbent assay and analyzed for correlation between FOXO3 levels and renal function.Results:(1)A total of 297 up-regulated DEGs and 1630 down-regulated DEGs were obtained after analysis of the GSE37171 dataset in the GEO database.(2)GO and KEGG enrichment analysis of the DEGs revealed that up-regulated DEGs mainly had biological functions such as hematopoiesis,maintenance of iron balance,coping with oxidative stress,and negative regulation of fibroblast proliferation.The analysis of cell components was mainly concentrated in the cytoplasmic matrix,cell membrane and endoplasmic reticulum.In terms of molecular function,they were enriched in oxygen binding,ferrous binding and ubiquitin protein ligase binding processes.They were mainly involved in ubiquitin-mediated proteolysis,HIF-1 signal transduction,endoplasmic reticulum protein processing and other signal transduction pathways.The down-regulated DEGs were mainly concentrated in intracellular signal transduction,m RNA processing,and protein phosphorylation.They were mainly involved in protein binding,RNA binding,protein kinase activity,and other molecular functions.They also played a role in endoplasmic reticulum protein processing,leukocyte transendothelial migration,Rap1 signal transduction,and other signaling pathways.(3)PPI network analysis on up-regulated DEGs enriched in biological functions.Key genes such as FOXO3,SOD2,RUNX3,FECH,PRDX2 were screened out using the Cyto Hubba plug-in of the Cytoscape platform.FOXO3 plays a pivotal role in the essential genes.(4)Compared with the control group,serum FOXO3 levels were elevated in patients with CKD stages 4-5 and were highest in CKD stage 5,with statistically significant differences(P < 0.001).(5)There was no significant difference in TC,TG,HDL-C,LDL-C,and UA among the three CKD groups(P > 0.05).Hb and eGFR in patients with CKD stage 3-5 gradually decreased with disease progression(P < 0.001).Scr,BUN,and Cys-C gradually increased with disease progression(P < 0.001).ALB in patients with CKD stages 4-5 was lower than that in CKD stage 3(P < 0.05),and there was no statistical difference between CKD stages 4-5(P > 0.05).Serum Ca of patients with CKD stage 5 was lower than patients with CKD stage 3(P < 0.05).Serum P of patients with CKD stage 4 was higher than patients with CKD stage 3(P < 0.001).There was no significant difference in the levels of Ca and P among patients with CKD stages 4-5(P > 0.05).(6)The level of FOXO3 was positively correlated with Scr,BUN,and Cys-C(P <0.05),and negatively correlated with Hb and eGFR(P < 0.05).There was no correlation with age,gender,BMI,ALB,TC,TG,HDL-C,LDL-C,UA,Ca,and P(P > 0.05).Multiple linear regression analysis showed that FOXO3 was ind-ependently associated with eGFR(P < 0.001).Conclusion:We found that serum FOXO3 levels gradually increased in patients with CKD stages3-5 and negatively correlated with patients’ glomerular filtration rate,suggesting that FOXO3 may play a role in the progression of CKD.