Background: Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide, whereas benign prostatic hyperplasia (BPH) is among the most prevalent non-malignant prostatic disorders. Differentiating between these two conditions remains challenging because of overlapping clinical manifestations and the limited specificity of currently available biomarkers. Methods: This retrospective study enrolled 200 male patients (53 PCa, 147 BPH) who underwent prostate biopsy or surgical resection based on pathological diagnosis. Clinical characteristics, laboratory parameters, and inflammatory indices were compared between the groups. Both univariate and multivariate logistic regression analyses were conducted to identify independent predictors. Nomograms were developed and validated through calibration curves, ROC analysis, and decision curve analysis (DCA). Results: PCa patients had significantly higher levels of inflammatory markers than BPH patients ( p < 0.05). In multivariate analysis, log2-SII (OR = 2.22, 95% CI: 1.13–4.37, p = 0.021) and log2-AISI (OR = 3.27, 95% CI: 1.83–5.85, p < 0.001) emerged as independent risk factors for PCa. The AISI-based model achieved superior diagnostic performance with an AUC of 0.878 (95% CI: 0.825–0.931) compared with the SII-based model (AUC = 0.855, 95% CI: 0.794–0.915). DCA showed greater clinical net benefit for the AISI model across a wide range of threshold probabilities. Conclusion: Blood inflammatory markers, particularly AISI, in combination with conventional biomarkers, offer enhanced diagnostic accuracy for differentiating BPH from PCa, representing a non-invasive and cost-effective approach for clinical decision-making.

Background: Radical nephrectomy (RN) and partial nephrectomy (PN) are common surgical treatments for T1 stage renal cell carcinoma (RCC). However, the long-term impact of these surgical approaches on prognosis and renal function remains an area of ongoing investigation. This study compared the effects of these procedures on prognosis and renal function. Methods: The data of 1,030 T1 stage RCC patients treated at Peking University Cancer Hospital & Institute between January 2014 and August 2022 were analyzed. The primary endpoints of the study were overall survival (OS) and cancer-specific survival (CSS). The secondary endpoints included the annual mean estimated glomerular filtration rate (eGFR) and the average annual eGFR change rates. Results: Based on a median follow-up time of 57 months, the OS and CSS rates were 96.6% and 98.5% in the overall cohort, respectively. The multivariate analysis identified age [hazard ratio (HR), 2.664; 95% confidence interval (CI): 1.147–6.192; P=0.02], tumor grade (HR, 2.247; 95% CI: 1.050–4.810; P=0.04), and surgical approach (HR, 2.585; 95% CI: 1.056–6.325; P=0.04) as adverse prognostic factors for OS, and age (HR, 4.603; 95% CI: 1.035–20.471; P=0.045) and tumor grade (HR, 4.972; 95% CI: 1.752–14.111; P=0.003) as adverse prognostic factors for CSS. Throughout the follow-up period, the eGFR of the RN patients showed a gradual increase, while that of the PN patients remained stable (P<0.001). Among the patients with preoperative diabetes, the eGFR of the RN patients decreased significantly compared to that of the PN patients (P=0.03). Conclusions: T1 stage RCC has a favorable prognosis with surgery, and PN is an oncologically safe option. A persistent eGFR difference was observed between the PN and RN groups, with RN showing a gradual upward trend. However, patients with pre-existing diabetes experienced a greater decline in renal function after RN, which highlights the advantages of PN for such patients.

The pronounced heterogeneity of bladder cancer (BLCA) drives divergent patient outcomes and therapy responses. Mitophagy, a pivotal cellular quality-control and metabolic mechanism, modulates the dynamics of the tumor microenvironment (TME). Its prognostic significance and potential for guiding precision oncology, however, remain incompletely defined. This investigation aimed to evaluate the translational utility of mitophagy-associated signatures for the risk stratification of BLCA, profiling of TME, and prediction of therapeutic response. Using The Cancer Genome Atlas (TCGA)-BLCA cohort, a prognostic signature was established via least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analyses. The robustness of the signature was externally validated using two independent cohorts from the Gene Expression Omnibus (GSE32894, n=224; GSE31684, n=93). A nomogram was established to estimate survival probability. A multi-faceted analysis of TME features was conducted to compare the subgroups, integrating three algorithms: Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), Tumor Immune Dysfunction and Exclusion (TIDE), and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE). Drug sensitivity and molecular alteration profiles were interrogated to identify potential personalized therapeutic avenues. A five-core-gene signature (NTN4, AKR1B1, FBXW7, MYH10, and IGF2BP3) was established. Across all cohorts, high-risk individuals exhibited notably shorter overall survival (OS) (TCGA-BLCA: P<0.001; GSE32894: P=0.003; GSE31684: P=0.03). The areas under the curves (AUCs) for 1-, 3-, and 5-year survival were 0.645–0.654 (TCGA-BLCA), 0.625–0.785 (GSE32894), and 0.567–0.651 (GSE31684). The TME analysis suggested that high-risk tumors were associated with elevated stromal scores, enrichment of M2 macrophages, and a predicted T-cell exclusion phenotype. Conversely, low-risk individuals exhibited an ‘immune-inflamed’ profile, marked by elevated microsatellite instability (MSI) and infiltration of CD8⁺ T cells. The profiling of drug sensitivity indicated that the low-risk subgroup might be more susceptible to cisplatin, whereas high-risk cases showed potential responsiveness to epidermal growth factor receptor (EGFR) and mechanistic target of rapamycin (mTOR) inhibitors. This research developed a mitophagy-derived signature that predicts survival and is associated with a potential ‘stromal barrier and immune-excluded’ phenotype underlying therapy resistance in high-risk BLCA. The model offers a stratification framework for therapeutic decisions. Standard chemotherapy or immune checkpoint blockade (ICB) may lead to benefits in the low-risk subgroup, whereas high-risk individuals likely require novel combinatorial strategies targeting microenvironmental remodeling. However, as these results represent predictive associations derived from public datasets, further experimental validation is warranted to confirm the underlying biological mechanisms.

Bladder cancer is one of the most common malignancies of the urinary system. Identifying new potential therapeutic targets and exploring molecular mechanisms are crucial for improving treatment and prognosis. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel 2, known to play a key role in various physiological and pathological processes, has an unclear function and mechanism of action in bladder cancer. We employed bioinformatics analysis and immunohistochemistry to assess the role of HCN2 in bladder cancer, integrating in vitro and in vivo models to evaluate the impact of HCN2 on cell behavior. Molecular interactions were characterized using immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. Our investigation revealed a significant upregulation of HCN2 in bladder cancer tissues, which was predictive of a poorer clinical outcome. Functionally, HCN2 knockdown in bladder cancer impeded cell proliferation, induced apoptosis, and curtailed migration and invasion. Mechanistically, the overexpression of HCN2 contributed to the translocation of the REST transcription factor into the nucleus and facilitated its binding to the BGN promoter for transcriptional activation of its expression. This regulatory mechanism was shown to suppress ferroptosis, a form of regulated cell death, thereby enhancing the proliferative and tumorigenesis of bladder cancer cells. This study uncovers the novel mechanism by which HCN2 regulates ferroptosis via the REST-BGN axis, affecting bladder cancer cell behavior, and provides new perspectives and strategies for future clinical treatment.