Development and validation of a novel nomogram predicting clinically significant prostate cancer in biopsy-naive men based on multi-institutional analysis.

BACKGROUND: Prediction of clinically significant prostate cancer (csPCa) is essential to select biopsy-naive patients for prostate biopsy. This study was to develop and validate a nomogram based on clinicodemographic parameters and exclude csPCa using prostate-specific antigen density (PSAD) stratification. METHODS: Independent predictors were determined via univariate and multivariate logistic analysis and adopted for developing a predictive nomogram, which was assessed in terms of discrimination, calibration, and net benefit. Different PSAD thresholds were used for deciding immediate biopsies in patients with Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions. RESULTS: A total of 932 consecutive patients who underwent ultrasound-guided transperineal cognitive biopsy were enrolled in our study. In the development cohort, age (odds ratio [OR], 1.075; 95% confidence interval [CI], 1.036-1.114), PSAD (OR, 6.003; 95% CI, 2.826-12.751), and PI-RADS (OR, 3.419; 95% CI, 2.453-4.766) were significant predictors for csPCa. On internal and external validation, this nomogram showed high areas under the curve of 0.943, 0.922, and 0.897, and low Brier scores of 0.092, 0.102, and 0.133 and insignificant unreliability tests of 0.713, 0.490, and 0.859, respectively. Decision curve analysis revealed this model could markedly improve clinical net benefit. The probability of excluding csPCa was 98.51% in patients with PI-RADS 3 lesions and PSAD <0.2 ng/ml2 . CONCLUSION: This novel nomogram including age, PSAD, and PI-RADS could be applied to accurately predict csPCa, and 44.08% of patients with equivocal imaging findings plus PSAD <0.2 ng/ml2 could safely forgo biopsy.

Identification of an immune subtype-related prognostic signature of clear cell renal cell carcinoma based on single-cell sequencing analysis.

Background: There is growing evidence that immune cells are strongly associated with the prognosis and treatment of clear cell renal cell carcinoma (ccRCC). Our aim is to construct an immune subtype-related model to predict the prognosis of ccRCC patients and to provide guidance for finding appropriate treatment strategies. Methods: Based on single-cell analysis of the GSE152938 dataset from the GEO database, we defined the immune subtype-related genes in ccRCC. Immediately afterwards, we used Cox regression and Lasso regression to build a prognostic model based on TCGA database. Then, we carried out a series of evaluation analyses around the model. Finally, we proved the role of VMP1 in ccRCC by cellular assays. Result: Initially, based on TCGA ccRCC patient data and GEO ccRCC single-cell data, we successfully constructed a prognostic model consisting of five genes. Survival analysis showed that the higher the risk score, the worse the prognosis. We also found that the model had high predictive accuracy for patient prognosis through ROC analysis. In addition, we found that patients in the high-risk group had stronger immune cell infiltration and higher levels of immune checkpoint gene expression. Finally, cellular experiments demonstrated that when the VMP1 gene was knocked down, 786-O cells showed reduced proliferation, migration, and invasion ability and increased levels of apoptosis. Conclusion: Our study can provide a reference for the diagnosis and treatment of patients with ccRCC.

Efficacy of peripheral electrical nerve stimulation on improvements of urodynamics and voiding diary in patients with neurogenic lower urinary tract dysfunction: a systematic review and meta-analysis.

BACKGROUND: Peripheral electrical nerve stimulation is a routinely recommended treatment for non-neurogenic overactive bladder but has not been approved for patients with neurogenic lower urinary tract dysfunction (NLUTD). This systematic review and meta-analysis was to elucidate the efficacy and safety of electrostimulation and thus provide firm evidence for treating NLUTD. MATERIALS AND METHODS: We systematically performed the literature search through PubMed, Web of Science, and Cochrane Library databases in March 2022. The eligible studies were identified across the inclusion criteria and the data on urodynamic outcomes, voiding diary parameters, and safety was collected to quantitatively synthesize the pooled mean differences (MDs) with 95% CIs. Subgroup analyses and sensitivity analyses were subsequently used to investigate the possible heterogeneity. This report was achieved in accordance with the preferred reporting items for systematic reviews and meta-analyses statement. RESULTS: A total of 10 studies involving 464 subjects and 8 studies with 400 patients were included for systematic review and meta-analysis, respectively. The pooled effect estimates indicated that electrostimulation could significantly improve urodynamic outcomes, including maximum cystometric capacity (MD=55.72, 95% CI 15.73, 95.72), maximum flow rate (MD=4.71, 95% CI 1.78, 7.65), maximal detrusor pressure (MD=-10.59, 95% CI -11.45, -9.73), voided volume (MD=58.14, 95% CI 42.97, 73.31), and post-void residual (MD=-32.46, 95% CI -46.63, -18.29); for voiding diary parameters, patients undergoing electrostimulation showed lower MDs of incontinence episodes per 24 h (MD=-2.45, 95% CI -4.69, -0.20) and overactive bladder symptom score (MD=-4.46, 95% CI -6.00, -2.91). In addition to surface redness and swelling, no stimulation-related severe adverse events were reported else. CONCLUSIONS: The current evidence demonstrated that peripheral electrical nerve stimulation might be effective and safe for managing NLUTD, whereas more reliable data from large-scale randomized controlled trials are necessary to strengthen this concept.

m6A Modification of Long Non-Coding RNA HNF1A-AS1 Facilitates Cell Cycle Progression in Colorectal Cancer via IGF2BP2-Mediated CCND1 mRNA Stabilization.

BACKGROUND: Long non-coding RNAs modulate tumor occurrence through different molecular mechanisms. It had been reported that HNF1A-AS1 (HNF1A Antisense RNA 1) was differently expressed in multiple tumors. The role of HNF1A-AS1 in colorectal cancer was less analyzed, and the mechanism of regulating the cell cycle has not been completely elucidated. METHODS: Differentially expressed lncRNAs were screened out from the TCGA database. HNF1A-AS1 was examined in CRC clinical samples and cell lines by RT-qPCR. CCK8 assay, colony formation assay, flow cytometry, transwell assays, tube forming assay and vivo experiments were performed to study the function of HNF1A-AS1 in CRC tumor progression. Bioinformatic analysis, luciferase report assay, RNA pull-down and RIP assays were carried out to explore proteins binding HNF1A-AS1 and the potential downstream targets. RESULTS: Our results showed that HNF1A-AS1 was upregulated in CRC and associated with unfavorable prognosis. HNF1A-AS1 promoted proliferation, migration and angiogenesis, accelerated cell cycle and reduced cell apoptosis in CRC. Bioinformatics prediction and further experiments proved that HNF1A-AS1 could promote CCND1 expression by suppressing PDCD4 or competitively sponging miR-93-5p. Meanwhile, METTL3 mediated HNF1A-AS1 m6A modification and affected its RNA stability. HNF1A-AS1/IGF2BP2/CCND1 may act as a complex to regulate the stability of CCND1. CONCLUSION: In summary, our result reveals the novel mechanism in which m6A-mediated HNF1A-AS1/IGF2BP2/CCND1 axis promotes CRC cell cycle progression, along with competitively sponging miR-93-5p to upregulate CCND1, demonstrating its significant role in cell cycle regulation and suggesting that HNF1A-AS1 may act as a potential prognostic marker of colorectal cancer in the future.

Neoadjuvant Chemohormonal Therapy in Prostate Cancer Before Radical Prostatectomy: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis was to investigate the effects of neoadjuvant chemohormonal therapy (NCHT) on patients with prostate cancer (PCa) before radical prostatectomy (RP) and attempt to provide meaningful evidence. Methods: A systematic search was performed using the PubMed, Web of Science, and Cochrane Library databases in February 2022 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relevant studies were critically screened and we extracted the data of demography, postoperative pathology, and survival to calculate the pooled effect sizes. Subgroup analyses and sensitivity analyses were used to explore the source of heterogeneity. Results: Six identified studies involving 1717 subjects were included according to the selection criteria. There was no significant difference between NCHT plus RP and RP alone groups regarding lymph node involvement (risk ratio [RR]=1.03, 95% confidence interval [CI]: 0.57-1.87, P=0.92). However, NCHT prior to RP significantly decreased the rates of positive surgical margin (PSM, RR=0.35, 95% CI: 0.22-0.55, P<0.0001) and seminal vesicle invasion (SVI, RR=0.78, 95% CI: 0.65-0.95, P=0.01), and increase pathological downstaging (RR=1.64, 95% CI: 1.17-2.29, P=0.004). Additionally, biochemical recurrence-free survival (BRFS) and overall survival (OS) were significantly prolonged under the administration of NCHT (HR=0.54, 95% CI: 0.34-0.85, P=0.008 and HR=0.67, 95% CI: 0.48-0.94, P=0.02, respectively). Conclusions: Compared to the RP alone group, patients with NCHT plus RP showed significant improvements in PSM, SVI, pathological downstaging, BRFS, and OS, whereas further multicenter randomized controlled trials are needed to consolidate this concept.

Breast cancer combined prognostic model based on lactate metabolism genes.

To investigate the impact of lactate metabolism genes, lactate metabolism-related genes (LMRG), and immune infiltrating cells on the prognosis of breast cancer. LMRG was identified via single-cell sequencing. Immune cell infiltration was obtained by the CIBERSORT method. The prognostic genes were chosen by cox regression and the least absolute selection operator approach. lactate metabolism-associated immune-infiltrating cells was determined by difference analysis. The GSE20685 dataset was used as an external validation cohort. The model's prognostic usefulness was evaluated utilizing survival, immunological microenvironment, and drug sensitivity assessments. NDUFAF6 was most associated with breast cancer prognosis. We obtained a total of 450 LMRG. SUSD3, IL18, MAL2, and CDKN1C comprised the Model2. NK cell activation was most relevant to lactate metabolism. The combined prognostic model outperformed the individual model, with the area under the curve ranging from 0.7 to 0.8 in all three cohorts. The lactate metabolism-related combination model assisted in evaluating breast cancer prognosis, providing new insights for treatment, particularly immunotherapy.