A Novel Therapeutic Strategy for Cervical Cancer: Research on Novel Biomarkers Associated with Mitophagy and Pyroptosis and Their Targeted Drug Development
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background: Mitophagy and pyroptosis exert intricate regulatory interactions in cellular physiological and pathological processes, yet their functional significance and clinical implications in cervical cancer remain incompletely elucidated. This study was designed to investigate whether these two biological processes and their associated genes can serve as reliable targets for the prediction, prevention, and personalized treatment of cervical cancer. Methods: Differentially expressed genes related to mitophagy and pyroptosis were initially screened using weighted gene co-expression network analysis and differential gene expression analysis, followed by machine learning-based identification of characteristic genes. Integrated bioinformatics analyses, including pathway enrichment, Gene Ontology annotation, survival correlation analysis, immune infiltration evaluation, and single-cell sequencing analysis, were performed. A competing endogenous RNA regulatory network was constructed. The OncoPredict R package was utilized to predict potential small-molecule therapeutic agents, with the binding stability of candidate drugs to target genes verified via molecular docking and molecular dynamics simulations. Results: The mitophagy-related gene DCN and pyroptosis-related genes TACR1, KIF23, and MEG3 exhibited significant diagnostic and prognostic predictive value in cervical cancer. Pseudotime trajectory analysis revealed dynamic expression fluctuations of DCN and MEG3 during disease progression, while KIF23 and TACR1 maintained relatively stable expression patterns. Cell-cell communication analysis demonstrated active crosstalk among multiple cell populations within cervical cancer lesions. Doxorubicin was identified as a promising therapeutic candidate, showing stable binding affinity to DCN, TACR1, and KIF23, and its therapeutic effects may be mediated through the regulation of mitophagy and pyroptosis signaling pathways. Conclusion: Mitophagy and pyroptosis synergistically drive the progression of cervical cancer. The four identified key genes possess robust prognostic utility, and doxorubicin exhibits considerable potential for personalized cervical cancer therapy by targeting these genes, thereby providing novel theoretical basis and clinical insights for the precise treatment of cervical cancer.