Journal of Translational Medicine最新文献

Objective: Cervical cancer remains a significant global health burden, with the molecular determinants of its progression and therapeutic resistance not fully elucidated. This study aimed to identify DNA damage-related genes with prognostic and functional significance.

Methods: Four cervical cancer GEO datasets were integrated and batch-corrected. Differential expression analysis and WGCNA were performed. Machine learning algorithms (LASSO, SVM, and Random Forest) were used to refine key genes. Functional roles of the pivotal gene SMC4 were investigated using in vitro experiments, including proliferation, colony formation, 3D spheroid assays, phalloidin staining, cell-cycle analysis, immunofluorescence, and analysis of DNA damage and immune-associated pathways under ionizing radiation.

Results: Integration of transcriptomic data revealed 16 candidate genes. Machine learning convergence identified five core genes (CCNB2, CDKN2A, CHEK1, TYMS, and SMC4), all of which were significantly upregulated in tumors. Among these, SMC4 was uniquely associated with poor overall and disease-specific survival. Functional assays demonstrated that SMC4 knockdown under ionizing radiation significantly inhibited cervical cancer cell proliferation, colony formation, invasion, and reduced S-phase cells, and impaired DNA damage repair. Mechanistically, SMC4 was found to upregulate SMAD3, activate NF-κB signaling, and promote PD-L1 expression. Single-cell analysis confirmed SMC4's predominant expression in epithelial cells and its association with an altered tumor immune context.

Conclusion: Our study identifies SMC4 as a regulator that promotes radioresistance and potentially modulates the tumor immune microenvironment in cervical cancer, likely by coordinating DNA damage repair and activating the SMAD3-NF-κB pathway. These findings suggest that SMC4 could be a potential therapeutic target for radiosensitization and a candidate biomarker for patient stratification.

Background: Noble gases xenon (Xe) and argon (Ar) emerge as promising therapeutic agents. Extensive studies have validated their efficacy across various models of organ injury, positioning them as novel candidates for clinical translation in critical care and perioperative medicine.

Main body: Xe and Ar exert protective effects through multiple mechanisms, including activation of hypoxia-inducible factor-1 (HIF-1) pathway, inhibition of regulated cell death pathways, such as apoptosis, necroptosis, ferroptosis, and pyroptosis, and suppression of pro-inflammatory signaling. By modulating these key signaling pathways, Xe and Ar have been shown to improve outcomes in neurological, cardiac, renal, and hepatic systems across diverse models of ischemia-reperfusion injury, traumatic brain injury, and systemic inflammation. Clinically, Xe has shown efficacy in anesthesia, neonatal neuroprotection, and cardiac arrest management. Ar, with greater availability and lower costs, holds promise for broader clinical use but remains in the early stage of translational research.

Conclusion: Xe and Ar represent novel biologically active gases with the potential to provide promising therapies in perioperative and clinical care medicine. Overcoming current limitations, such as a lack of standardized delivery systems and optimized dosing strategies, is key to uncovering their clinical application.