Investigating the causal relationship between major depressive disorder and benign prostatic hyperplasia: a bidirectional Mendelian randomisation study.

BACKGROUND: Evidence from various cohort studies indicate a potential association between depressive disorder and benign prostatic hyperplasia (BPH), yet findings are inconsistent. This study employs bidirectional two-sample Mendelian randomisation (MR) analysis to explore the causal relationship between BPH and major depressive disorder (MDD). METHODS: Genetic variants strongly associated with MDD were extracted as instrumental variables conducted by the Psychiatric Genomics Consortium (PGC). Two sets of genetic variants associated with BPH were extracted from the recent FinnGen and Medical Research Council-Integrative Epidemiology Unit Consortium of BPH as the discovery and replication stages, respectively. Bidirectional MR analysis employed methods such as inverse variance weighted, MR-Egger, weighted median, maximum likelihood, and weighted mode. The inverse variance weighted method was primarily used to evaluate the causal relationship. RESULTS: MR analysis in both the discovery and replication stages showed a significant causal relationship between MDD and the risk of BPH (discovery stages, odds ratio (OR) = 1.1146, 95% CI 1.0058-1.2353, P = 0.03852; replication stage, OR: 1.0042, 95% CI 1.0019-1.0065, P = 0.0004). No causal relationship was found between BPH and MDD risk in the reverse MR analysis. CONCLUSIONS: Our findings highlight a significant association between MDD and an increased risk of BPH development. Further investigation is needed to elucidate the underlying mechanisms linking depression and BPH.

CAB39 modulates epithelial-mesenchymal transition through NF-κB signaling activation, enhancing invasion, and metastasis in bladder cancer.

Bladder cancer (BC), the predominant urological malignancy in men, exhibits complex molecular underpinnings contributing to its progression. This investigation aims to elucidate the expression dynamics of calcium-binding protein 39 (CAB39) in both healthy and cancerous tissues and to explore its functional role in the epithelial-mesenchymal transition (EMT) within human bladder cancer contexts. Utilizing immunohistochemistry and quantitative reverse transcription analyses, we assessed CAB39 expression across BC specimens and cell lines. Further, we implemented wound healing, cell invasion, and CCK-8 proliferation assays in CAB39-knockdown cell lines, alongside a nude mouse xenograft model, to gauge the impact of diminished CAB39 expression on the invasive, migratory, and proliferative capacities of BC cells. Our gene set enrichment analysis probed into the repertoire of genes augmented by increased CAB39 expression in BC cells, with subsequent validation via western blotting. Our findings reveal a pronounced overexpression of CAB39 in both BC tissues and cellular models, inversely correlated with disease prognosis. Remarkably, the oncogenic trajectory of bladder cancer was mitigated upon the establishment of shRNA-mediated CAB39 knockdown in vitro and in vivo, effectively reversing the cancer's invasive and metastatic behaviors and curbing tumorigenesis in xenograft models. Hence, CAB39 emerges as a critical biomarker for bladder cancer progression, significantly implicated in facilitating EMT via the upregulation of neural cadherin (N-cadherin) and the suppression of epithelial cadherin through NF-κB signaling pathways. CU-T12-9 effectively overturned the downregulation of p65-NF-kB and N-cadherin, key elements involved in EMT and cell motility, induced by CAB39 knockdown. This study underscores CAB39's pivotal role in bladder cancer pathophysiology and its potential as a therapeutic target.

A novel anoikis-related gene signature identifies LYPD1 as a novel therapy target for bladder cancer.

Bladder cancer (BLCA) is a malignant tumor associated with unfavorable outcomes. Studies suggest that anoikis plays a crucial role in tumor progression and cancer cell metastasis. However, its specific role in bladder cancer remains poorly understood. Our objective was to identify anoikis-related genes (ARGs) and subsequently construct a risk model to assess their potential for predicting the prognosis of bladder cancer.The transcriptome data and clinical data of BLCA patients were sourced from The Cancer Genome Atlas and GEO database. We then performed the differential expression analysis to screen differentially expressed ARGs. Subsequently, we conducted non-negative matrix factorization (NMF) clustering analysis to establish molecular subtypes based on the differentially expressed ARGs. The CIBERSORT algorithm was used to estimate the quantification of different cell infiltration in BLCA tumor microenviroment. A prognostic risk model containing 7 ARGs was established using Lasso-Cox regression analysis. The nomogram was built for predicting the survival probability of BLCA patients. To determine the drug sensitivity of each sample from the high- and low-risk groups, the R package "pRRophetic" was performed. Finally, the role of LYPD1 was explored in BLCA cell lines.We identified 90 differential expression ARGs and NMF clustering categorizated the BLCA patientss into two distinct groups (cluster A and B). Patients in cluster A had a better prognosis than those in cluster B. Then, we established a ARGs risk model including CALR, FASN, FOSL1, JUN, LYPD1, MST1R, and SATB1, which was validated in the train and test set. The results suggested overall survival rate was much higher in low risk group than high risk group. The cox regression analysis, ROC curve analysis, and nomogram collectively demonstrated that the risk model served as an independent prognostic factor. The high risk group had a higher level TME scores compared to the low risk group. Furthermore, LYPD1 was low expression in BLCA cells and overexpression of LYPD1 inhibits the prolifearation, migration and invasion.In the current study, we have identified differential expression ARGs and constructed a risk model with the promise for guiding prognostic predictions and provided a therapeutic target for patients with BLCA.