Anoikis in prostate cancer bone metastasis gene signatures and therapeutic implications.

Background: Bone metastasis from prostate cancer severely impacts patient outcomes and quality of life. Anoikis, a form of programmed cell death triggered by the loss of cell-matrix interactions, plays a critical role in cancer progression. However, its precise relationship with prostate cancer-induced bone metastasis remains unclear. This study aims to elucidate this relationship, focusing on anoikis-related gene signatures, molecular pathways, and therapeutic implications. Methods: We used the TCGA-PRAD dataset for training, with MSKCC and GSE70769 as validation cohorts. To evaluate immunotherapy efficacy, we examined IMvigor 210 and GSE91016 datasets, and GSE137829 provided single-cell insights into prostate cancer. Specific anoikis-related genes (ARGs) were identified, and Random Survival Forest analysis and multivariate Cox regression were employed to develop anoikis-linked features. The 'clustanoikisProfilanoikis' and 'GSEA' packages were used to explore potential ARG-related pathways. Results: Analyzing 553 samples from TCGA, 231 from MSKCC, 94 from GSE70769, and single-cell data from 6 prostate cancer patients (GSE137829), we constructed a prognostic model based on 9 ARGs. GSVA revealed upregulation of carcinogenic pathways, including epithelial-mesenchymal transition, E2F targets, and angiogenesis, with downregulation of metabolic pathways. Significant differences in somatic mutations were observed between cohorts, with a positive correlation between anoikis scores and tumor mutational burden (TMB). Immune landscape analysis suggested high-risk patients might benefit more from chemotherapy than immunotherapy based on their risk score. Single-cell analysis indicated overactivation of carcinogenic pathways in the high anoikis score group. Conclusion: This study elucidates the complex interplay between anoikis and bone metastasis in prostate cancer. Our findings highlight the critical role of anoikis in metastatic progression, enhancing the understanding of key biomarkers and molecular dynamics. The identified anoikis-related gene signatures and disrupted pathways offer promising avenues for predictive and therapeutic strategies in prostate cancer management.

Overexpression of DUSP26 gene suppressed the proliferation, migration, and invasion of human prostate cancer cells.

Prostate cancer (PCa) is threatening the health of millions of people, the pathological mechanism of prostate cancer has not been fully elaborated, and needs to be further explored. Here, we found that the expression of DUSP26 is dramatically suppressed, and a positive connection of its expression with PCa prognosis was also observed. In vitro, overexpression of DUSP26 significantly inhibited the proliferative, migrative, and invasive capacities of PC3 cells, DUSP26 silencing presented opposite results. Tumor formation experiments in subcutaneous nude mice demonstrated that DUSP26 overexpression could significantly suppress PC3 growth in vivo. Moreover, the mechanism of DUSP26 gene and PCa was discovered by RNA-Seq analysis. We found that DUSP26 significantly inhibited MAPK signaling pathway activation, and further experiments displayed that DUSP26 could impair TAK1, p38, and JNK phosphorylation. Interestingly, treatment with the TAK1 inhibitor (iTAK1) attenuated the effect of DUSP26 on PC3 cells. Together, these results suggested that DUSP26 may serve as a novel therapeutic target for PC3 cell type PCa, the underlying mechanism may be through TAK1-JNK/p38 signaling.

Pretreatment of the urethral mucosa at the tip of the prostate: a retrospective review in preventing stress urinary incontinence after thulium laser enucleation of the prostate.

Objective: Explore the clinical application value of urethral mucosal pretreatment at the tip of the prostate in preventing stress urinary incontinence (SUI) after thulium laser enucleation of the prostate (ThuLEP). Methods: Eighty-seven patients with benign prostatic hyperplasia (BPH) treated with ThuLEP from June 2021 to December 2022 were divided into two groups. Of these, 42 patients (group A) underwent conventional ThuLEP and 45 patients (group B) were enucleated after pretreatment of the urethral mucosa. At the tip of the prostate, pretreatment of the urethral mucosa consisted of pushing the gland separately on both sides at the level of the verumontanum and cutting off the mucosa near the external urethral sphincter clockwise and counterclockwise. The perioperative and postoperative follow-up indicators [operation time, hemoglobin reduction, complications, Qmax, International Prostate Symptom Score (IPSS), quality of life (QoL), and post-void residual (PVR) volume] of the two groups of patients were collected and compared. All patients were followed up 1 month after surgery. Results: All 87 procedures were successfully completed. There was no significant difference in age and gland size between the two groups (P > 0.05). There was no significant difference between operating time and hemoglobin reduction in the two groups (P > 0.05). The Qmax, IPSS, QOL, and PVR volume were significantly improved postoperatively in both groups (P < 0.05). Temporary SUI occurred in both groups [12 cases (28.5%) in group A and 3 cases (6.7%) in group B (P < 0.05)]. There was no significant difference in the incidence of infection and urethral stricture between the two groups (P > 0.05). Conclusion: Pretreatment of the urethral mucosa before ThuLEP for BPH significantly reduces the incidence of SUI after surgery. This technique, which preconditions the apical urethral mucosa of the prostate, is safe and effective, has few complications, and is worthy of clinical application.

Prognosis and diagnosis of prostate cancer based on hypergraph regularization sparse least partial squares regression algorithm.

BACKGROUND: Prostate cancer (PCa) is a malignant tumor of the male reproductive system, and its incidence has increased significantly in recent years. This study aimed to further identify candidate biomarkers with prognostic and diagnostic significance by integrating gene expression and DNA methylation data from PCa patients through association analysis. MATERIAL AND METHODS: To this end, this paper proposes a sparse partial least squares regression algorithm based on hypergraph regularization (HR-SPLS) by integrating and clustering two kinds of data. Next, module 2, with the most significant weight, was selected for further analysis according to the weight of each module related to DNA methylation and mRNAs. Based on the DNA methylation sites in module 2, this paper uses multiple machine learning methods to construct a PCa diagnosis-related model of 10-DNA methylation sites. RESULTS: The results of Receiver Operating Characteristic (ROC) analysis showed that the DNA methylation-related diagnostic model we constructed could diagnose PCa patients with high accuracy. Subsequently, based on the mRNAs in module 2, we constructed a prognostic model for 7-mRNAs (MYH11, ACTG2, DDR2, CDC42EP3, MARCKSL1, LMOD1, and MYLK) using multivariate Cox regression analysis. The prognostic model could predict the disease free survival of PCa patients with moderate to high accuracy (area under the curve (AUC) =0.761). In addition, Gene Set EnrichmentAnalysis (GSEA) and immune analysis indicated that the prognosis of patients in the risk group might be related to immune cell infiltration. CONCLUSIONS: Our findings may provide new methods and insights for identifying disease-related biomarkers by integrating DNA methylation and gene expression data.

Integrating single-cell RNA-sequencing and bulk RNA-sequencing data to explore the role of mitophagy-related genes in prostate cancer.

Prostate cancer (PCa) is the most common malignancy of the male urinary system. Mitophagy, as a type of autophagy, can remove damaged mitochondria in cells. Mitophagy-related genes (MRGs) have been shown to play critical roles in the development of PCa. To this end, based on the comprehensive analysis of RNA-seq and scRNA-seq data of PCa samples and their controls, this paper identified PCa subtypes and constructed a prognostic model. In this paper, we downloaded scRNA-seq and RNA-seq data from Gene Expression Omnibus (GEO) and TCGA database. Based on the R package "Seurat" to process the scRNA-seq data, a total of five cell types were identified. Each cell population was scored based on the R package "AUCell" and using the intersection genes between MRGs and each cell population. The B cell population was then identified as a high-scoring cell population. Differentially expressed genes in RNA-seq data were identified based on the R package "limma" and intersected with previously intersected genes. Then, based on univariate Cox regression analysis and Lasso-Cox regression analysis, the prognostic genes were screened, and the risk model was constructed (composed of ADH5, CAT, BCAT2, DCXR, OGT, and FUS). The model is validated on internal and external test sets. Independent prognostic analysis identified age, N stage, and risk score as independent prognostic factors. This paper's risk models and prognostic genes can provide a reference for developing novel therapeutic targets for PCa.

Laparoscopic ureteroneocystostomy with bladder flap for benign ureteral stenosis: our initial experience.

To present our experience with laparoscopic ureteroneocystostomy with bladder flap (LUCBF) for treating benign ureteral stenosis and evaluate its feasibility and efficacy. The clinical data of 27 patients with benign ureteral stenosis who underwent LUCBF were retrospectively analyzed. After identification and excision of the ureteral stenosis segment, the healthy ureteral stump was dissected and incised longitudinally. A U-shaped or spiral bladder flap was harvested from the anterolateral bladder wall for ureteroplasty. All patients underwent LUCBF successfully, including 14 patients were combined with psoas hitch technique, between 90 and 220 min (median, 155 min). The median length of ureteral defect was 6 cm (range, 5-17 cm). The median blood loss was 40 ml (20-150 ml). The median indwelling time of double-J stent was 8 weeks (range, 4-8 weeks). Five patients (10.6%) suffered postoperative complications during the follow-up period (range, 12-48 months), including fever, hematuria, urinary tract infection and recurrent stenosis. The success rate was 96.3% (26/27). Patients with long ureter defects had longer operative time and more blood loss than short ureter defects. LUCBF was a safe and feasible technique for benign ureteral stenosis. Long ureter defect was related to longer operative time and more blood loss.

Lysosomal-Associated Transmembrane Protein 5 Promotes Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most aggressive and deadly cancer of the urinary system and is regulated by multiple signaling pathways. However, the specific molecular mechanisms underlying ccRCC have not been fully studied or demonstrated. This study aimed to elucidate the function of lysosomal-associated transmembrane protein 5 (LAPTM5) in ccRCC cell lines and animal models and determine the potential underlying mechanisms. Our results demonstrated that LAPTM5 expression in patients with ccRCC was significantly higher in the tumor group than that in the adjacent nontumor group. Moreover, LAPTM5 promoted proliferation, migration, and invasion of ccRCC cells through the gain and loss of the function of LAPTM5 in 786-0 and Caki-1 cell lines. Similar results regarding LAPTM5 overexpression were obtained in BALB/c nude mice. In addition, LAPTM5 activated the Jun N-terminal kinase (JNK)/p38 signaling cascade by interacting with Ras-related C3 botulinum toxin substrate 1 (RAC1). Treatment with an RAC1 inhibitor eliminated the effects of LAPTM5 in ccRCC. In conclusion, these results indicate that LAPTM5 may be a new therapeutic target for ccRCC via activation of the RAC1-JNK/p38 axis.

Clinical potential of the Hippo-YAP pathway in bladder cancer.

Bladder cancer (BC) is one of the world's most frequent cancers. Surgery coupled with adjuvant platinum-based chemotherapy is the current standard of therapy for BC. However, a high proportion of patients progressed to chemotherapy-resistant or even neoplasm recurrence. Hence, identifying novel treatment targets is critical for clinical treatment. Current studies indicated that the Hippo-YAP pathway plays a crucial in regulating the survival of cancer stem cells (CSCs), which is related to the progression and reoccurrence of a variety of cancers. In this review, we summarize the evidence that Hippo-YAP mediates the occurrence, progression and chemotherapy resistance in BC, as well as the role of the Hippo-YAP pathway in regulating bladder cancer stem-like cells (BCSCs). Finally, the clinical potential of Hippo-YAP in the treatment of BC was prospected.

Associations between inflammasome-related gene NLRP3 Polymorphisms (rs10754558 and rs35829419) and risk of bladder cancer in a Chinese population.

BACKGROUND: NLRP3 inflammasome as a component of immune system has been found related to several cancers, but no study has assessed NLRP3 polymorphisms on risk of bladder cancer (BC). We aim to investigate whether NLRP3 polymorphisms are associated with the risk and clinical features of bladder cancer (BC) in a Chinese population. METHODS: Genotype frequency of two commonly studied NLRP3 SNPs (rs10754558 and rs35829419) was examined in 154 patients with BC and the 308 healthy controls. NLRP3 gene polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The distribution frequencies of GG, AG+GG, GG, and G allele in NLRP3 (rs10754558) genotypes were significantly different between case and control group (OR = 2.296, P = .022; OR = 1.598, P = .020; OR = 1.998, P = .049; OR = 1.557, P = .006), but no statistical difference existed for rs35829419. Among smokers and alcohol drinkers, for rs10754558, individuals with AG, GG, and GG+AG genotypes had a higher BC risk compared with individuals with AA; for rs35829419, individuals with variant genotypes (AG and GG+AG) had a stronger risk of developing BC compared with individuals with AA (all P < .05). In stratified analyses of tumor size and tumor node metastasis, AG or GG genotypes of rs10754558 and rs35829419 SNPs were associated with BC risk (both P < .05). CONCLUSION: NLRP3 polymorphisms (rs10754558 and rs35829419) were related to BC risk and tumor size and lymph node metastasis, especially among smokers and alcohol drinkers.

MiR-193a-3p functions as a tumour suppressor in human aldosterone-producing adrenocortical adenoma by down-regulating CYP11B2.

The mechanism of aldosterone-producing adrenocortical adenoma (APA) pathogenesis and the role of microRNAs (miRNAs) in APA pathogenesis have not been completely clarified. We examined the expression and function of miR-140-3p, miR-193a-3p and miR-22-3p, which have binding sites in CYP11B2. Expression of miRNAs and CYP11B2 mRNA was measured by quantitative reverse transcription PCR (qRT-PCR). Cell proliferation was monitored by colorimetric analysis, and cell apoptosis and cell cycle progression were analysed by flow cytometry. ELISA was carried out to detect aldosterone levels in cell culture supernatants. Luciferase reporter assays, qRT-PCR and Western blotting were performed to identify CYP11B2 as a target of miR-193a-3p. Of the three miRNAs examined, miR-193a-3p exhibited a significant decrease and CYP11B2 mRNA exhibited a significant increase in expression in APA compared with adjacent normal adrenal gland tissue. Transfection of miR-193a-3p mimic into the human adrenocortical cell line H295R showed that elevated miR-193a-3p expression inhibits proliferation and aldosterone secretion, induces G1-phase arrest and promotes apoptosis in H295R cells. Furthermore, in luciferase reporter assays, overexpression of miR-193a-3p in H295R cells significantly reduced the luciferase activity of the wild-type CYP11B2 3'-UTR construct, which could be reversed by mutation of the miR-193a-3p-binding site. Moreover, miR-193a-3p overexpression downregulated CYP11B2 mRNA and protein expression. Finally, overexpression of CYP11B2 diminished the effects of miR-193a-3p on H295R cells. Taken together, our results suggest that CYP11B2 levels may be modulated by miR-193a-3p in APA, which could explain, at least partially, why downregulation of miR-193a-3p during APA formation may promote cell growth and suppress apoptosis.