Welcome to visit Zhongnan Medical Journal Press Series journal website!

Bioinformatics-based screening and analysis of potential biomarkers in pediatric ulcerative colitis

Published on Mar. 02, 2024Total Views: 877 timesTotal Downloads: 2518 timesDownloadMobile

Author: ZOU Qiufeng ZOU Jiaying LI Lijuan FANG Xiaoling HUANG Wenjuan

Affiliation: Department of Neonatology, The 924st Hospital of People’s Liberation Army, Guilin 541000, Guangxi Province, China

Keywords: Pediatric Ulcerative colitis Gene Bioinformatics Biomarkers

DOI: 10.12173/j.issn.1004-5511.202302036

Reference: Zou QF, Zou JY, Li LJ, Fang XL, Huang WJ. Bioinformatics-based screening and analysis of potential biomarkers in pediatric ulcerative colitis[J]. Yixue Xinzhi Zazhi, 2024, 34(2): 149-156. DOI: 10.12173/j.issn.1004-5511.202302036.[Article in Chinese]

  • Abstract
  • Full-text
  • References
Abstract

Objective  Bioinformatics analysis was performed to screen and identify the underlying gene biomarkers in pediatric ulcerative colitis (UC) patients.

Methods  GSE126124 dataset, the mRNA expression profile of inflammatory bowel disease, was downloaded from the gene expression omnibus (GEO) database. GEO2R was utilized to obtain differentially expressed genes (DEGs) between pediatric ulcerative colitis tissues and corresponding normal tissues in the dataset. Functional and pathway enrichment analysis and protein-protein interaction analysis of DEGs were conducted using the DAVID and STRING database. The Cytoscape software was used to analyze protein-protein interaction network and hub genes. At last, the KEGG analyzed the biology and pathway enrichment of hub genes.

Results  A total of 153 DEGs were obtained, including 92 up-regulated and 61 down-regulated genes. Functional and pathway enrichment analysis showed that up-regulated DEGs were significantly enriched in the external stimulus, staphylococcus aureus infection and IL-17 signaling pathway. Functional and pathway enrichment analysis showed that down-regulated DEGs were significantly enriched in the transport, membrane composition and metabolic pathway. Furthermore, 10 DEGs were considered hub genes, including Cxcl1, Cxcl2, Cxcl10, Cxcr2, Il1rn, Fcgr3a, Cxcr1, S100a12, Ido1 and Ccl24. Pathway enrichment analysis showed that hub genes were significantly enriched in the chemokines, the interaction between viral proteins and cytokines and receptors, epithelial cells infected by Helicobacter pylori, IL-17 and TNF.

Conclusion  This research found 153 DEGs, in which 10 hub genes may play an important role in the occurrence and development of pediatric UC.

Full-text
Please download the PDF version to read the full text: download
References

1.Ordás I, Eckmann L, Talamini M, et al. Ulcerative colitis[J]. Lancet, 2012, 380(9853): 1606-1619. DOI: 10.1016/s0140-6736(12)60150-0.

2.da Silva BC, Lyra AC, Rocha R, et al. Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis[J]. World J Gastroenterol, 2014, 20(28): 9458-9467. DOI: 10.3748/wjg.v20.i28.9458.

3.Guinet-Charpentier C, Champigneulle J, Williet N, et al. The association of autoimmune diseases with pediatric ulcerative colitis does not influence its disease course[J]. Scand J Gastroenterol, 2016, 51(1): 33-40. DOI: 10.3109/00365521.2015.1058415.

4.Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology[J]. Lancet, 2007, 369(9573): 1627-1640. DOI: 10.1016/s0140-6736(07)60750-8.

5.Van Limbergen J, Russell RK, Drummond HE, et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease[J]. Gastroenterology, 2008, 135(4): 1114-1122. DOI: 10.1053/j.gastro.2008.06.081.

6.Malaty HM, Mehta S, Abraham B, et al. The natural course of inflammatory bowel disease-indeterminate from childhood to adulthood: within a 25 year period[J]. Clin Exp Gastroenterol, 2013, 6: 115-121. DOI: 10.2147/ceg.S44700.

7.Buderus S, Scholz D, Behrens R, et al. Inflammatory bowel disease in pediatric patients: characteristics of newly diagnosed patients from the CEDATA-GPGE Registry[J]. Dtsch Arztebl Int, 2015, 112(8): 121-127. DOI: 10.3238/arztebl.2015.0121.

8.Zaidi D, Bording-Jorgensen M, Huynh HQ, et al. Increased epithelial gap density in the noninflamed duodenum of children with inflammatory bowel diseases[J]. J Pediatr Gastroenterol Nutr, 2016, 63(6): 644-650. DOI: 10.1097/mpg.0000000000001182.

9.Furey TS, Sethupathy P, Sheikh SZ. Redefining the IBDs using genome-scale molecular phenotyping [J]. Nat Rev Gastroenterol Hepatol, 2019, 16(5): 296-311. DOI: 10.1038/s41575-019-0118-x.

10.Kammermeier J, Morris MA, Garrick V, et al. Management of Crohn's disease[J]. Arch Dis Child, 2016, 101(5): 475-480. DOI: 10.1136/archdischild-2014-307217.

11.Heyman MB, Kirschner BS, Gold BD, et al. Children with early-onset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry[J]. J Pediatr, 2005, 146(1): 35-40. DOI: 10.1016/j.jpeds.2004.08.043.

12.Fell JM, Muhammed R, Spray C, et al. Management of ulcerative colitis[J]. Arch Dis Child, 2016, 101(5): 469-474. DOI: 10.1136/archdischild-2014-307218.

13.李娜, 叶梅. 炎症性肠病药物治疗的沿革与前瞻 [J]. 医学新知, 2023, 34(1): 99-106. [Li N, Ye M, History and prospect of medical treatment of inflammatory bowel disease[J] Yixue Xinzhi Zazhi, 2023, 34(1): 99-106.] . DOI: 10.12173/j.issn.1004-5511. 202212024.

14.Kaiser GC, Yan F, Polk DB. Mesalamine blocks tumor necrosis factor growth inhibition and nuclear factor kappaB activation in mouse colonocytes[J]. Gastroenterology, 1999, 116(3): 602-609. DOI: 10.1016/s0016-5085(99)70182-4.

15.Yan F, Polk DB. Aminosalicylic acid inhibits IkappaB kinase alpha phosphorylation of IkappaBalpha in mouse intestinal epithelial cells[J]. J Biol Chem, 1999, 274(51): 36631-36636. DOI: 10.1074/jbc.274.51.36631.

16.Barnes PJ. Molecular mechanisms and cellular effects of glucocorticosteroids[J]. Immunol Allergy Clin North Am, 2005, 25(3): 451-468. DOI: 10.1016/j.iac.2005.05.003.

17.Berends SE, Strik AS, Löwenberg M, et al. Clinical pharmacokinetic and pharmacodynamic considerations in the treatment of ulcerative colitis[J]. Clin Pharmacokinet, 2019, 58(1): 15-37. DOI: 10.1007/s40262-018-0676-z.

18.Danese S. Mechanisms of action of infliximab in inflammatory bowel disease: an anti-inflammatory multitasker[J]. Dig Liver Dis, 2008, 40(Suppl 2): S225-S228. DOI: 10.1016/s1590-8658(08)60530-7.

19.Chhibba T, Ma C. Is there room for immunomodulators in ulcerative colitis?[J]. Expert Opin Biol Ther, 2020, 20(4): 379-390. DOI: 10.1080/14712598.2020.1708896.

20.Thomas CW, Myhre GM, Tschumper R, et al. Selective inhibition of inflammatory gene expression in activated T lymphocytes: a mechanism of immune suppression by thiopurines[J]. J Pharmacol Exp Ther, 2005, 312(2): 537- 545. DOI: 10.1124/jpet.104.074815.

21.Feuerstein JD, Moss AC, Farraye FA. Ulcerative Colitis[J]. Mayo Clin Proc, 2019, 94(7): 1357-1373. DOI: 10.1016/j.mayocp.2019.01.018.

22.Noble CL, Abbas AR, Cornelius J, et al. Regional variation in gene expression in the healthy colon is dysregulated in ulcerative colitis[J]. Gut, 2008, 57(10): 1398-1405. DOI: 10.1136/gut.2008.148395.

23.Xiu MX, Liu YM, Chen GY, et al. Identifying hub genes, key pathways and immune cell infiltration characteristics in pediatric and adult ulcerative colitis by integrated bioinformatic analysis[J]. Dig Dis Sci, 2021, 66(9): 3002-3014. DOI: 10.1007/s10620-020-06611-w.

24.Ungaro R, Mehandru S, Allen PB, et al. Ulcerative colitis[J]. Lancet, 2017, 389(10080): 1756-1770. DOI: 10.1016/s0140-6736(16)32126-2.

25.Zimmerman NP, Vongsa RA, Wendt MK, et al. Chemokines and chemokine receptors in mucosal homeostasis at the intestinal epithelial barrier in inflammatory bowel disease[J]. Inflamm Bowel Dis, 2008, 14(7): 1000-1011. DOI: 10.1002/ibd.20480.

26.Markiewski MM, Nilsson B, Ekdahl KN, et al. Complement and coagulation: strangers or partners in crime?[J]. Trends Immunol, 2007, 28(4): 184-192. DOI: 10.1016/j.it.2007.02.006.

27.Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine[J]. Chest, 1992, 101(6): 1644-1655. DOI: 10.1378/chest.101.6.1644.

28.Xu M, Kong Y, Chen N, et al. Identification of immune-related gene signature and prediction of cerna network in active ulcerative colitis[J]. Front Immunol, 2022, 13: 855645. DOI: 10.3389/fimmu.2022.855645.

29.Walana W, Ye Y, Li M, et al. IL-8 antagonist, CXCL8(3- 72)K11R/G31P coupled with probiotic exhibit variably enhanced therapeutic potential in ameliorating ulcerative colitis[J]. Biomed Pharmacother, 2018, 103: 253-261. DOI: 10.1016/j.biopha.2018.04.008.

30.Kishida K, Kohyama M, Kurashima Y, et al. Negative regulation of DSS-induced experimental colitis by PILRα[J]. Int Immunol, 2015, 27(6): 307-314. DOI: 10.1093/intimm/dxv004.

31.Ranganathan P, Jayakumar C, Manicassamy S, et al. CXCR2 knockout mice are protected against DSS-colitis-induced acute kidney injury and inflammation[J]. Am J Physiol Renal Physiol, 2013, 305(10): F1422-F1427. DOI: 10.1152/ajprenal.00319.2013.

32.Shi X, Yu J, Lu C, et al. Screening of the shared pathogenic genes of ulcerative colitis and colorectal cancer by integrated bioinformatics analysis[J]. J Cell Mol Med, 2023: 28(5): e17878. DOI: 10.1111/jcmm.17878.

33.Romero-Cara P, Torres-Moreno D, Pedregosa J, et al. A FCGR3A polymorphism predicts anti-drug antibodies in chronic inflammatory bowel disease patients treated with anti-TNF[J]. Int J Med Sci, 2018, 15(1): 10-15. DOI: 10.7150/ijms.22812.

34.Chen ZA, Sun YF, Wang QX, et al. Integrated analysis of multiple microarray studies to identify novel gene signatures in ulcerative colitis[J]. Front Genet, 2021, 12:  697514. DOI: 10.3389/fgene.2021.697514.

35.Zhang Q, Zuo Y, Xu M. The correlation of serum Vaspin, S100A12 and PCT levels with the severity of ulcerative colitis and its clinical significance[J]. Am J Transl Res, 2021, 13(7): 7914-7920. PMID: 34377270. https://pubmed.ncbi.nlm.nih.gov/34377270/.