MAPK9 as a therapeutic target:unveiling ferroptosis in localized prostate cancer progression

Background:Ferroptosis,a lipid peroxidation-mediated programmed cell death,is closely linked to tumor development,including prostate cancer(PCa).Despite established connections between ferroptosis and PCa,a comprehensive investigation is essential for understanding its impact on patient prognosis.Methods:A risk model incorporating four ferroptosis-related genes was developed and validated.Elevated risk scores correlated with an increased likelihood of biochemical recurrence(BCR),diminished immune infiltration,and adverse clinicopathological characteristics.To corroborate these results,we performed validation analyses utilizing datasets from both the Cancer Genome Atlas Cohort(TCGA)and the Gene Expression Synthesis Cohort(GEO).Moreover,we conducted further investigations into the pivotal gene identified in our model to explore its impact on tumor characteristics through cell proliferation and invasion assays,as well as animal studies conducted in vivo.Additionally,we conducted further experiments involving ferroptosis-related analysis to validate its association with ferroptosis.Results:The risk model demonstrated exceptional predictive capabilities for prognosis and therapeutic outcomes in PCa patients.Mitogen-activated protein kinase 9(MAPK9)emerged as a crucial gene within the model.In vivo and in vitro experiments explored MAPK9’s role in ferroptosis and its influence on tumor migration and proliferation.Conclusion:The findings provide a novel perspective for advancing ferroptosis exploration in PCa,bridging basic research and clinical applications.

A novel mouse model simulating transurethral laser vaporization prostatectomy

Benign prostatic hyperplasia(BPH)is a common disease in elderly men,and transurethral laser prostatectomy(TULP)has been widely used in the clinic to remove bladder outlet obstruction caused by BPH.Previous animal models for wound repair after prostatectomy have many limitations,and there have been no previous reports of a mouse model of TULP.Therefore,this study aimed to establish a novel mouse model of TULP.Twelve healthy adult Kunming(KM)mice received transurethral laser vaporization prostatectomy with a 200-μm thulium laser.The mice were sacrificed,and wound specimens from the prostatic urethra and bladder neck were harvested at 1 day,3 days,5 days,and 7 days after surgery.Hematoxylin-eosin(HE)and immunohistochemistry were applied to confirm the establishment of the mouse TULP model.One day after the surgery,urothelium expressing uroplakin(UPK)was absent in the urethral wound site,and a large number of necrotic tissues were found in the wound site.There was no UPK-positive urothelium in the wound 3 days after surgery.At 5 days after surgery,monolayer urothelium expressing UPK was found in the wound site,indicating that the re-epithelization of the wound had been completed.On the 7th day after surgery,there were multiple layers of urothelium with UPK expression,indicating that the repair was completed.It is feasible to establish a mouse TULP model by using a microcystoscope system and a 200-μm thulium laser.