Machine-learning prediction of a novel diagnostic model using mitochondria-related genes for patients with bladder cancer

Abstract

Abstract Bladder cancer (BC) is the ninth most-common cancer worldwide and it is associated with high morbidity and mortality. Mitochondrial Dysfunction is involved in the progression of BC. This study aimed to developed a novel diagnostic model based on mitochondria-related genes (MRGs) for BC patients using Machine Learning. In this study, we analyzed GSE13507 datasets and identified 752 DE-MRGs in BC specimens. Functional enrichment analysis uncovered the significant roles of 752 DE-MRGs in key processes such as cellular and organ development, as well as gene regulation. The analysis revealed the crucial functions of these genes in transcriptional regulation and protein-DNA interactions. Then, we performed LASSO and SVM-RFE, and identified four critical diagnostic genes including GLRX2, NMT1, OXSM and TRAF3IP3. Based on the above four genes, we developed a novel diagnostic model whose diagnostic value was confirmed in GSE13507, GSE3167 and GSE37816 datasets. Moreover, we reported the expressing pattern of GLRX2, NMT1, OXSM and TRAF3IP3 in BC samples. Immune cell infiltration analysis revealed that the four genes were associated with several immune cells. Finally, we performed RT-PCR and confirmed NMT1 was highly expressed in BC cells. Functional experiments revealed that knockdown of NMT1 suppressed the proliferation of BC cells. Overall, we have formulated a diagnostic potential that offered a comprehensive framework for delving into the underlying mechanisms of BC. Before proceeding with clinical implementation, it is essential to undertake further investigative efforts to validate its diagnostic effectiveness in BC patients.

Keywords

• Mitochondria
• Bladder cancer
• Diagnostic model
• Machine Learning
• Immune infiltration
• GEO datasets