Identification of Key Immune-related Genes and Immune Infiltration in Diabetic Nephropathy Based on Machine Learning Algorithms

Overview

Journal IET Syst Biol

Publisher Wiley

Specialty Biology

Date 2023 Mar 15

PMID 36919187

Authors

Yue Sun

Weiran Dai

Wenwen He

Affiliations

Soon will be listed here.

Abstract

Background: Diabetic nephropathy (DN) is a complication of diabetes. This study aimed to identify potential diagnostic markers of DN and explore the significance of immune cell infiltration in this pathology.

Methods: The GSE30528, GSE96804, and GSE1009 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by merging the GSE30528 and GSE96804 datasets. Enrichment analyses of the DEGs were performed. A LASSO regression model, support vector machine recursive feature elimination analysis and random forest analysis methods were performed to identify candidate biomarkers. The CIBERSORT algorithm was utilised to compare immune infiltration between DN and normal controls.

Results: In total, 115 DEGs were obtained. The enrichment analysis showed that the DEGs were prominent in immune and inflammatory responses. The DEGs were closely related to kidney disease, urinary system disease, kidney cancer etc. CXCR2, DUSP1, and LPL were recognised as diagnostic markers of DN. The immune cell infiltration analysis indicated that DN patients contained a higher ratio of memory B cells, gamma delta T cells, M1 macrophages, M2 macrophages etc. cells than normal people.

Conclusion: Immune cell infiltration is important for the occurrence of DN. CXCR2, DUSP1, and LPL may become novel diagnostic markers of DN.

Citing Articles

Identification of key immune-related genes and potential therapeutic drugs in diabetic nephropathy based on machine learning algorithms.

Guo C, Wang W, Dong Y, Han Y BMC Med Genomics. 2024; 17(1):220.

PMID: 39187837 PMC: 11348758. DOI: 10.1186/s12920-024-01995-4.

Identification of key immune-related genes and immune infiltration in diabetic nephropathy based on machine learning algorithms.

Sun Y, Dai W, He W IET Syst Biol. 2023; 17(3):95-106.

PMID: 36919187 PMC: 10280611. DOI: 10.1049/syb2.12061.

References

Zhang X, Zhou M, Guo Y, Song Z, Liu B . 1,25-Dihydroxyvitamin D₃ Promotes High Glucose-Induced M1 Macrophage Switching to M2 via the VDR-PPARγ Signaling Pathway. Biomed Res Int. 2015; 2015:157834. PMC: 4417570. DOI: 10.1155/2015/157834. View

Wang X, Yao B, Wang Y, Fan X, Wang S, Niu A . Macrophage Cyclooxygenase-2 Protects Against Development of Diabetic Nephropathy. Diabetes. 2016; 66(2):494-504. PMC: 5248989. DOI: 10.2337/db16-0773. View

Heudes D, Mandet C, Belair M, Michel O, Perdereau B, Bariety J . Early glomerular macrophage recruitment in streptozotocin-induced diabetic rats. Diabetes. 2000; 49(3):466-75. DOI: 10.2337/diabetes.49.3.466. View

Liu P, Li X, Lv W, Xu Z . Inhibition of CXCL1-CXCR2 axis ameliorates cisplatin-induced acute kidney injury by mediating inflammatory response. Biomed Pharmacother. 2019; 122:109693. DOI: 10.1016/j.biopha.2019.109693. View

Yu K, Li D, Xu F, Guo H, Feng F, Ding Y . IDO1 as a new immune biomarker for diabetic nephropathy and its correlation with immune cell infiltration. Int Immunopharmacol. 2021; 94:107446. DOI: 10.1016/j.intimp.2021.107446. View

Roth R, Le A, Zhang L, Kahn M, Samuel V, Shulman G . MAPK phosphatase-1 facilitates the loss of oxidative myofibers associated with obesity in mice. J Clin Invest. 2009; 119(12):3817-29. PMC: 2786792. DOI: 10.1172/JCI39054. View

Litman-Zawadzka A, Lukaszewicz-Zajac M, Gryko M, Kulczynska-Przybik A, Kedra B, Mroczko B . Specific Receptors for the Chemokines CXCR2 and CXCR4 in Pancreatic Cancer. Int J Mol Sci. 2020; 21(17). PMC: 7504436. DOI: 10.3390/ijms21176193. View

Alegre-Diaz J, Herrington W, Lopez-Cervantes M, Gnatiuc L, Ramirez R, Hill M . Diabetes and Cause-Specific Mortality in Mexico City. N Engl J Med. 2016; 375(20):1961-1971. PMC: 5215048. DOI: 10.1056/NEJMoa1605368. View

Samanta A, Oppenheim J, Matsushima K . Identification and characterization of specific receptors for monocyte-derived neutrophil chemotactic factor (MDNCF) on human neutrophils. J Exp Med. 1989; 169(3):1185-9. PMC: 2189253. DOI: 10.1084/jem.169.3.1185. View

10.

Wilson P, Wu H, Kirita Y, Uchimura K, Ledru N, Rennke H . The single-cell transcriptomic landscape of early human diabetic nephropathy. Proc Natl Acad Sci U S A. 2019; 116(39):19619-19625. PMC: 6765272. DOI: 10.1073/pnas.1908706116. View

11.

Li Y, Li Y, Yang T, Wang M . Dioscin attenuates oxLDL uptake and the inflammatory reaction of dendritic cells under high glucose conditions by blocking p38 MAPK. Mol Med Rep. 2019; 21(1):304-310. PMC: 6896274. DOI: 10.3892/mmr.2019.10806. View

12.

Garfinkel A, Nilsson-Ehle P, Schotz M . Regulation of lipoprotein lipase. Induction by insulin. Biochim Biophys Acta. 1976; 424(2):264-73. DOI: 10.1016/0005-2760(76)90194-6. View

13.

Scirica B, Mosenzon O, Bhatt D, Udell J, Steg P, McGuire D . Cardiovascular Outcomes According to Urinary Albumin and Kidney Disease in Patients With Type 2 Diabetes at High Cardiovascular Risk: Observations From the SAVOR-TIMI 53 Trial. JAMA Cardiol. 2017; 3(2):155-163. PMC: 6594440. DOI: 10.1001/jamacardio.2017.4228. View

14.

Ramasamy R, Yan S, Herold K, Clynes R, Schmidt A . Receptor for advanced glycation end products: fundamental roles in the inflammatory response: winding the way to the pathogenesis of endothelial dysfunction and atherosclerosis. Ann N Y Acad Sci. 2008; 1126:7-13. PMC: 3049155. DOI: 10.1196/annals.1433.056. View

15.

Antonacci Y, Toppi J, Mattia D, Pietrabissa A, Astolfi L . Single-trial Connectivity Estimation through the Least Absolute Shrinkage and Selection Operator. Annu Int Conf IEEE Eng Med Biol Soc. 2020; 2019:6422-6425. DOI: 10.1109/EMBC.2019.8857909. View

16.

Lin J, Cheng A, Cheng K, Deng Q, Zhang S, Lan Z . New Insights into the Mechanisms of Pyroptosis and Implications for Diabetic Kidney Disease. Int J Mol Sci. 2020; 21(19). PMC: 7583981. DOI: 10.3390/ijms21197057. View

17.

Sanford D, Belt B, Panni R, Mayer A, Deshpande A, Carpenter D . Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res. 2013; 19(13):3404-15. PMC: 3700620. DOI: 10.1158/1078-0432.CCR-13-0525. View

18.

Gluhovschi C, Gluhovschi G, Petrica L, Timar R, Velciov S, Ionita I . Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy. J Diabetes Res. 2016; 2016:4626125. PMC: 4927990. DOI: 10.1155/2016/4626125. View

19.

Loretelli C, Rocchio F, DAddio F, Ben Nasr M, Castillo-Leon E, Dellepiane S . The IL-8-CXCR1/2 axis contributes to diabetic kidney disease. Metabolism. 2021; 121:154804. DOI: 10.1016/j.metabol.2021.154804. View

20.

Saraheimo M, Teppo A, Forsblom C, Fagerudd J, Groop P . Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients. Diabetologia. 2003; 46(10):1402-7. DOI: 10.1007/s00125-003-1194-5. View