Exploring the Molecular Mechanisms and Shared Gene Signatures Between Systemic Lupus Erythematosus and Bladder Urothelial Carcinoma

Abstract

Kongjia Wang,1 Shufei Wang,2 Yixin Ding,3 Zengshun Kou,1 Bo Jiang,1 Sichuan Hou1 1Department of Urology, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 2College of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 3Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Bo Jiang; Sichuan Hou, Email [email protected]; [email protected]: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with increased susceptibility to cancer, including bladder urothelial carcinoma (BLCA). This study investigates the shared molecular mechanisms and gene signatures between SLE and BLCA, shedding light on potential biomarkers and therapeutic targets.Methods: We compiled gene datasets related to SLE and BLCA from various databases and identified common genes. Differential gene expression analysis, protein-protein interaction networks, and hub gene identification were performed. We studied functional enrichment, immune infiltration, and transcription factor/miRNA regulation networks. We also explored gene-disease interactions and protein-chemical/drug networks. Hub gene expression levels and diagnostic values were validated in TCGA and GEO databases. Prognostic analysis was performed on the core gene MMP9 in the TCGA-BLCA database to study its prognostic value. Finally, the mRNA expression of MMP9 was verified in bladder cancer cell lines and BLCA patient blood. The diagnostic value of MMP9 for BLCA was verified by receiver operating characteristic(ROC) curve analysis of the expression of MMP9 in patients’ blood.Results: We identified 524 common genes between SLE and BLCA, enriched in pathways related to apoptosis and cytokine regulation. Immune infiltration analysis for two diseases. Transcription factors and microRNAs were implicated in regulating these common genes. The gene-disease network linked hub genes with various diseases, emphasizing their roles in autoimmune disease and cancer. Protein-chemical/drug networks highlighted potential treatment options. Finally, our study found that MMP9 is a potential therapeutic target with diagnostic and prognostic value and Immune-related biomarkers in patients with BLCA and SLE.Conclusion: Our study reveals shared molecular mechanisms, genetic signatures, and immune infiltrates between SLE and BLCA. MMP9 emerges as a potential diagnostic and prognostic biomarker in BLCA, warranting further investigation. These findings provide insights into the pathogenesis of SLE-associated BLCA and may guide future research and therapeutic strategies.Keywords: systemic lupus erythematosus, bladder urothelial carcinoma, gene signatures, immune response, MMP9

Keywords

• systemic lupus erythematosus
• bladder urothelial carcinoma
• gene signatures
• immune response
• mmp9