Sains Malaysiana 53(12)(2024): 3895-3906

http://doi.org/10.17576/jsm-2024-5312-05

 

Unveiling Common Pathways and Potential Drug Targets for Ulcerative Colitis and IgG4-Related Disease through Bioinformatics Analysis

(Mendedahkan Laluan Biasa dan Sasaran Dadah Berpotensi untuk Kolitis Ulseratif dan Penyakit Berkaitan IgG4 melalui Analisis Bioinformatik)

 

QUAN LIAO^1#, HONGJIAN ZHANG^1#, FANGYUAN ZHOU¹, HUASHENG LIN², XIONGWEI ZHENG¹, ZHIYUN WENG³, KAIYUE LI⁴, ZHENG WAN¹, & HENG PAN¹*

 

¹Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen City, 361000, Fujian, China
²Guangdong Medical University, Dongguan City, 523000, Guangdong, China.
³Department of Hematology, Yueqing People’s Hospital, Yueqing City, 325600, Zhejiang, China
⁴Department of Obstetrics and Gynecology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou City, 510405, Guangdong, China

 

Received: 16 July 2024/Accepted: 8 October 2024

 

^#These authors contribute equally to this work

 

Abstract

Patients with ulcerative colitis (UC) are at an increased risk of developing IgG4 related diseases (IgG4-RD). However, the molecular mechanisms are not known. This study aimed to investigate the potential molecular mechanisms and drugs to treat both UC and IgG4-RD. GSE42911 and GSE40568 datasets were intersected to generate common differentially expressed genes (DEGs). The DEGs were then subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. After a protein-protein interaction network (PPI) analysis, hub genes and transcriptional regulators (TFs) were tracked. Finally, potential therapeutic drugs were predicted by the DGIDB drug database. A total of 212 common DEGs were identified in between UC and IgG4-RD. Functional enrichment revealed DEGs enriched in ‘cytoplasm’, and ‘RNA binding’. Furthermore, KEGG pathway analysis identified significant enrichment in ‘Hippo signaling’. The PPI network was enriched with 162 genes/nodes and 532 edges. Additionally, hub genes and associated with 41 TFs and 18 miRNAs were found. Finally, 16 potential drugs targeted to four hub genes were found. In summary, these findings provide novel insights into the pathophysiology of UC and IgG4-RD, highlighting potential molecular targets and drug candidates for therapeutic intervention. The identified drugs could pave the way for targeted therapies, potentially improving clinical outcomes for patients suffering from these conditions and offering a new direction for treatment strategies in both UC and IgG4-RD.

 

Keywords: Bioinformatics; drug molecule; IgG4 related diseases; protein-protein interaction; ulcerative colitis

 

Abstrak

Pesakit dengan kolitis ulseratif (UC) mempunyai risiko yang lebih tinggi untuk mendapat penyakit berkaitan IgG4 (IgG4-RD). Walau bagaimanapun, mekanisme molekulnya tidak diketahui. Penyelidikan ini bertujuan untuk mengkaji mekanisme molekul dan dadah yang berpotensi untuk merawat kedua-dua UC dan IgG4-RD. Dataset GSE42911 dan GSE40568 bersilang untuk menghasilkan gen biasa terekspres secara berbeza (DEG). DEG kemudiannya tertakluk kepada analisis Ontologi Gen (GO) dan Ensiklopedia Gen dan Genom Kyoto (KEGG). Selepas analisis rangkaian interaksi protein-protein (PPI), gen hab dan pengawal selia transkrip (TF) telah dijejaki. Akhirnya, dadah terapeutik yang berpotensi telah diramalkan oleh pangkalan data dadah DGIDB. Sebanyak 212 DEG biasa dikenal pasti antara UC dan IgG4-RD. Pengayaan berfungsi menunjukkan DEG yang diperkaya dalam ‘sitoplasma’ dan ‘pengikatan RNA’. Tambahan pula, analisis laluan KEGG mengenal pasti pengayaan yang ketara dalam ‘Isyarat Hippo’. Rangkaian PPI telah diperkaya dengan 162 gen/nod dan 532 segi. Selain itu, gen hab dan dikaitkan dengan 41 TF dan 18 miRNA ditemui. Akhirnya, 16 dadah berpotensi yang disasarkan kepada empat gen hab ditemui. Ringkasnya, penemuan ini memberikan pandangan baharu tentang patofisiologi UC dan IgG4-RD, menonjolkan sasaran molekul yang berpotensi dan calon dadah untuk campur tangan terapeutik. Dadah yang dikenal pasti boleh membuka jalan untuk terapi bersasar yang berpotensi meningkatkan hasil klinikal untuk pesakit yang mengalami keadaan ini dan menawarkan arah baharu untuk strategi rawatan dalam kedua-dua UC dan IgG4-RD.

 

Kata kunci: Bioinformatik; interaksi protein-protein; kolitis ulseratif; molekul dadah; penyakit berkaitan IgG4

 

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*Corresponding author; email: pheng84@163.com