To detect potential pathways and target genes in infantile Pompe patients using computational analysis

To detect potential pathways and target genes in infantile Pompe patients using computational analysis Aynur Karadağ Gürel Department of Medical Biology, School of Medicine, Usak University, Usak, Turkey http://orcid.org/0000-0002-5499-5168 Selçuk Gürel Department of Pediatrics, School of Medicine, Bahcesehir University, İstanbul, Turkey http://orcid.org/0000-0001-5300-9795

Introduction: Pompe disease (PD) is a disease caused by pathogenic variations in the GAA gene known as glycogen storage disease type II, characterized by heart hypertrophy, respiratory failure, and muscle hypotonia, leading to premature death if not treated early. The only treatment option, enzyme replacement therapy (ERT), significantly improves the prognosis for some patients while failing to help others. In this study, the determination of key genes involved in the response to ERT and potential molecular mechanisms were investigated. Methods: Gene Expression Omnibus (GEO) data, accession number GSE38680, containing samples of biceps and quadriceps muscles was used. Expression array data were analyzed using BRB-Array Tools. Biceps group patients did not receive ERT, while quadriceps received treatment with rhGAA at 0, 12, and 52 weeks. Differentially expressed genes (DEGs) were deeply analyzed by DAVID, GO, KEGG and STRING online analyses, respectively. Results: A total of 1727 genes in the biceps group and 1198 genes in the quadriceps group are expressed differently. It was observed that DEGs were enriched in the group that responded poorly to ERT in the 52nd week. Genes frequently changed in the weak response group; the expression of 530 genes increased and 1245 genes decreased compared to 0 and 12 weeks. The GO analysis demonstrated that the DEGs were mainly involved in vascular smooth muscle contraction, lysosomes, autophagy, regulation of actin cytoskeleton, inflammatory response, and the WNT signaling pathway. We also discovered that the WNT signaling pathway is highly correlated with DEGs. Several DEGs, such as WNT11, WNT5A, CTNNB1, M6PR, MYL12A, VCL, TLN, FYN, YES1, and BCL2, may be important in elucidating the mechanisms underlying poor response to ERT. Conclusion: Early diagnosis and treatment of PD are very important for the clinic of the disease. As a result, it suggests that the enriched genes and new pathways emerging as a result of the analysis may help identify the group that responds poorly to treatment and the outcome of the treatment. Obtained genes and pathways in neonatal screening will guide diagnosis and treatment.
01 22 2022 01 22 2022 89 105 1 10.34172/crossmark_policy bi.tbzmed.ac.ir false Tabriz University of Medical Sciences Tabriz University of Medical Sciences 2020-10-20 2021-02-13 2022-01-22 10.34172/bi.2022.23467 20220328130753 https://bi.tbzmed.ac.ir/Article/bi-23467 https://bi.tbzmed.ac.ir/PDF/bi-12-89.pdf https://bi.tbzmed.ac.ir/PDF/bi-12-89.pdf https://bi.tbzmed.ac.ir/PDF/bi-12-89.pdf https://bi.tbzmed.ac.ir/PDF/bi-12-89.pdf https://bi.tbzmed.ac.ir/PDF/bi-12-89.pdf 10.1016/j.ymgme.2017.10.008 10.1007/s13311-018-0655-y 10.1203/PDR.0b013e3181b24e94 10.1002/mus.22329 10.109701.gim.0000218152.87434.f3 10.1152/physiolgenomics.00075.2016 10.1016/j.jpeds.2010.11.053 10.109700125817-200103000-00007 10.1016/j.nmd.2004.10.009 10.1038/gim.2012.44 10.1016/j.ymgme.2017.12.435 10.31486/toj.18.0049 10.1056/NEJMoa0909859 10.1212/01.wnl.0000251268.41188.04 10.1016/j.ymgme.2009.08.003 10.1016/j.ymgme.2012.05.004 Cancer Informatics Analysis of Gene Expression Data Using BRB-Array Tools Simon R 3 11 2007 10.1177/117693510700300022 10.1074/mcp.O115.048777 10.1007/s12035-019-01820-5 10.1002/14651858.CD011539.pub2 10.1542/peds.113.5.e448 10.1002/ana.20019 10.1056/NEJMc0806809 10.1002/mus.20896 10.1002/ana.20807 Mol Genet Metab Enzyme replacement therapy in the mouse model of Pompe disease Raben N 80 159 2003 10.1016/j.ymgme.2003.08.022 10.4161/auto.2984 10.1016/j.ymgme.2011.02.006 10.1016/j.cell.2007.10.018 10.1002/humu.21566 10.1007/s10545-010-9179-2 10.1007/s00415-009-5275-3 10.1016/j.nurt.2008.08.009 10.1111/ene.13285 10.1186/1750-1172-8-90 10.1186/s13023-018-0771-0 10.2310/JIM.0b013e3181c5e074 10.1074/jbc.M112.427484 10.1016/j.bbrc.2006.08.106 10.1038/s41598-017-14063-y 10.1242/dmm.010389 10.1016/j.biocel.2005.04.018 10.1152/ajpregu.00469.2004 10.1038/s41436-018-0103-8 10.1111/dmcn.13600 10.1016/j.arr.2016.07.005 10.3390/diseases4040040 10.1016/j.ymgme.2012.04.013 10.1542/peds.2008-3667 10.1097/GIM.0b013e31819d0996 10.1007/s10545-011-9360-2 10.1097/GIM.0b013e3181a87867