Background: Ferroptosis is a new type of programmed cell death which has been reported to be involved in the development of various cancers. In this study, we attempted to explore the possible links between ferroptosis and prostate cancer (PCa), and a novel ferroptosis-related gene prognostic index (FGPI) was constructed to predict biochemical recurrence (BCR) and radiation resistance for PCa patients undergoing radical radiotherapy (RRT). Moreover, the tumor immune microenvironment (TME) of PCa was analyzed.Methods: We merged four GEO datasets by removing batch effects. All analyses were conducted with R version 3.6.3 and its suitable packages. Cytoscape 3.8.2 was used to establish a network of transcriptional factor and competing endogenous RNA.Results: We established the FGPI based on ACSL3 and EPAS1. We observed that FGPI was an independent risk factor of BCR for PCa patients (HR: 3.03; 95% CI: 1.68–5.48), consistent with the result of internal validation (HR: 3.44; 95% CI: 1.68–7.05). Furthermore, FGPI showed high ability to identify radiation resistance (AUC: 0.963; 95% CI: 0.882–1.00). LncRNA PART1 was significantly associated with BCR and might modulate the mRNA expression of EPAS1 and ACSL3 through interactions with 60 miRNAs. Gene set enrichment analysis indicated that FGPI was enriched in epithelial–mesenchymal transition, allograft rejection, TGF beta signaling pathway, and ECM receptor interaction. Immune checkpoint and m6A analyses showed that PD-L2, CD96, and METTL14 were differentially expressed between BCR and no BCR groups, among which CD96 was significantly associated with BCR-free survival (HR: 1.79; 95% CI: 1.06–3.03). We observed that cancer-related fibroblasts (CAFs), macrophages, stromal score, immune score, estimate score, and tumor purity were differentially expressed between BCR and no BCR groups and closely related to BCR-free survival (HRs were 2.17, 1.79, 2.20, 1.93, 1.92, and 0.52 for cancer-related fibroblasts, macrophages, stromal score, immune score, estimate score, and tumor purity, respectively). Moreover, cancer-related fibroblasts (coefficient: 0.20), stromal score (coefficient: 0.14), immune score (coefficient: 0.14), estimate score (coefficient: 0.15), and tumor purity (coefficient: −0.15) were significantly related to FGPI, among which higher positive correlation between cancer-related fibroblasts and FGPI was observed.Conclusion: We found that FGPI based on ACSL3 and EPAS1 might be used to predict BCR and radiation resistance for PCa patients. CD96 and PD-L2 might be a possible target for drug action. Besides, we highlighted the importance of immune evasion in the process of BCR.

Purpose: Our aim was to assess the efficacy and safety of miniaturized percutaneous nephrolithotomy (mPCNL) versus standard PCNL (sPCNL) to provide higher-level evidence. Materials and Methods: Eligible randomized controlled trials were identified from electronic databases. The data analysis was performed by the Cochrane Collaboration's software RevMan 5.3. Results: A total of 1,219 patients from 9 articles published between 2004 and 2019 were included. Compared with those who received sPCNL, patients who received mPCNL experienced a higher stone-free rate (SFR) (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.03-1.99; p=0.03), lower transfusion rates (OR, 0.33; 95% CI, 0.17-0.63; p=0.0007), and lower drops in hemoglobin (mean difference [MD],-0.72; 95% CI,-1.04 to-0.40; p<0.00001), but the operative time seemed to be significantly longer (MD, 10.98; 95% CI, 3.64-18.32; p=0.003). Of note, there was no significant difference between the two groups regarding the SFR (p=0.09) for renal calculi ≥2 cm. In addition, the meta-analysis results showed no significant differences between the groups regarding urine leakage (p=0.60), postoperative fever (p=0.71), impaired ventilation (p=0.97), or total complications (p=0.29) with no heterogeneity between trials. These results remain unaffected with regard to renal calculi ≥2 cm. Conclusions: Our findings suggested that mPCNL had a higher SFR than sPCNL and there was no significant difference between the two groups for renal stones ≥2 cm. Besides, mPCNL tended to be associated with significantly less bleeding and a lower transfusion rate, but the duration of the procedure seemed to be significantly longer.

To evaluate the efficiency and safety of preoperative double-J stent placement for patients undergoing ureteroscopic lithotripsy. Eligible studies were identified from electronic databases (PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews). All analyses were performed by the Review Manager 5.3 (The Cochrane Collaboration, Oxford, UK). Stone-free rate (SFR) was regarded as primary outcome. Second outcomes, including operation time, complication rates as well as major complication rates were also assessed. A total of 11,239 patients (2605 with and 8634 without preoperative stent) from nine retrospective studies were included. Our pooled analysis showed that SFR was significantly higher in patients with a preoperative stent than those without a stent (OR 1.60, 95% CI 1.19-2.15, p = 0.002). Operation time was not significantly different between stented and non-stented groups (OR - 0.89, 95% CI - 5.79-4.01, p = 0.72). No significant differences of complication rates were observed between stented and non-stented groups (OR 0.94, 95% CI 0.67-1.33, p = 0.73). Furthermore, major complication rates were not significantly different between two groups, either (OR 1.07, 95% CI 0.43-2.70, p = 0.88). Generally, preoperative double-J stent placement significantly improved SFR of patients undergoing ureteroscopic lithotripsy. Operation time, complication rates, as well as major complication rates, were similar between stented and non-stented groups. However, the effect of preoperative double-J stent placement for different locations and burden of stones is unclear, more high-quality studies should be anticipated.

Background: The underutilization of additional supportive muscles is one of the potential reasons for suboptimal efficacy of conventional pelvic floor muscle training (CPFMT). The present study concentrates on any advantage of advanced pelvic floor muscle training (APFMT) in patients with urinary incontinence (UI) after radical prostatectomy (RP). Methods: Literature search was conducted on PubMed, Embase, Cochrane Library and Web of Science from database inception to February 2020. The data analysis was performed by the Cochrane Collaboration's software RevMan 5.3. Results: Both APFMT and CPFMT groups indicates superiority over baseline in terms of pad number, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score, pad weight at short-term follow-up, and PFME and PFMS at intermediate-term follow-up. No adverse events were reported in all included studies. Patients receiving APFMT had a similar attrition rate to those receiving CPFMT (18/236 vs. 22/282, P=0.61). Compared to CPFMT group, APFMT group provided intermediateterm advantages in terms of pad number (MD: −0.75, 95% CI: −1.36 to −0.14; P=0.02), ICIQ-SF score (MD:

BackgroundCurrently, the impact of the circadian rhythm on the tumorigenesis and progression of prostate cancer (PCA) has yet to be understood. In this study, we first established a novel nomogram to predict PCA progression based on circadian clock (CIC)-related genes and provided insights into the tumor immune microenvironment.MethodsThe TCGA and Genecards databases were used to identify potential candidate genes. Lasso and Cox regression analyses were applied to develop a CIC-related gene signature. The tumor immune microenvironment was evaluated through appropriate statistical methods and the GSCALite database.ResultsTen genes were identified to construct a gene signature to predict progression probability for patients with PCA. Patients with high-risk scores were more prone to progress than those with low-risk scores (hazard ratio (HR): 4.11, 95% CI: 2.66-6.37; risk score cut-off: 1.194). CLOCK, PER (1, 2, 3), CRY2, NPAS2, RORA, and ARNTL showed a higher correlation with anti-oncogenes, while CSNK1D and CSNK1E presented a greater relationship with oncogenes. Overall, patients with higher risk scores showed lower mRNA expression of PER1, PER2, and CRY2 and higher expression of CSNK1E. In general, tumor samples presented higher infiltration levels of macrophages, T cells and myeloid dendritic cells than normal samples. In addition, tumor samples had higher immune scores, lower stroma scores and lower microenvironment scores than normal samples. Notably, patients with higher risk scores were associated with significantly lower levels of neutrophils, NK cells, T helper type 1, and mast cells. There was a positive correlation between the risk score and the tumor mutation burden (TMB) score, and patients with higher TMB scores were more prone to progress than those with lower TMB scores. Likewise, we observed similar results regarding the correlation between the microsatellite instability (MSI) score and the risk score and the impact of the MSI score on the progression-free interval. We observed that anti-oncogenes presented a significantly positive correlation with PD-L1, PD-L2, TIGIT and SIGLEC15, especially PD-L2.ConclusionWe identified ten prognosis-related genes as a promising tool for risk stratification in PCA patients from the fresh perspective of CIC.

BackgroundWe aimed to construct and validate an energy metabolism-related gene prognostic index (EMRGPI) to predict biochemical recurrence (BCR) in patients undergoing radical prostatectomy.MethodsWe used Lasso and COX regression analysis to orchestrate the EMRGPI in the TCGA database, and the prognostic value of EMRGPI was further validated externally using the GSE46602. All analyses were conducted with R version 3.6.3 and its suitable packages.ResultsSDC1 and ADH1B were finally used to construct the risk formula. We classified the 430 tumor patients in the TCGA database into two groups, and patients in the high-risk group had a higher risk of BCR than those in the low-risk group (HR: 1.98, 95%CI: 1.18-3.32, p=0.01). Moreover, in the GSE46602, we confirmed that the BCR risk in the high-risk group was 3.86 times higher than that in the low-risk group (95%CI: 1.61-9.24, p=0.001). We found that patients in the high-risk group had significantly higher proportions of residual tumor, older age, and T stage. SDC1 and ADH1B were significantly expressed low in the normal tissues when compared to the tumor tissues, which were opposite at the protein level. The spearman analysis showed that EMRGPI was significantly associated with B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score, and estimate score. In addition, the EMRGPI was positively associated with the 54 immune checkpoints, among which CD80, ADORA2A, CD160, and TNFRSF25 were significantly related to the BCR-free survival of PCa patients undergoing RP.ConclusionsThe EMRGPI established in this study might serve as an independent risk factor for PCa patients undergoing radical prostatectomy.

Background Senescent cells have been identified in the aging prostate, and the senescence-associated secretory phenotype might be linked to prostate cancer (PCa). Thus, we established a cellular senescence-related gene prognostic index (CSGPI) to predict metastasis and radioresistance in PCa. Methods We used Lasso and Cox regression analysis to establish the CSGPI. Clinical correlation, external validation, functional enrichment analysis, drug and cell line analysis, and tumor immune environment analysis were conducted. All analyses were conducted with R version 3.6.3 and its suitable packages. Results We used ALCAM and ALDH2 to establish the CSGPI risk score. High-risk patients experienced a higher risk of metastasis than their counterparts (HR: 10.37, 95% CI 4.50–23.93, p < 0.001), consistent with the results in the TCGA database (HR: 1.60, 95% CI 1.03–2.47, p = 0.038). Furthermore, CSGPI had high diagnostic accuracy distinguishing radioresistance from no radioresistance (AUC: 0.938, 95% CI 0.834–1.000). GSEA showed that high-risk patients were highly associated with apoptosis, cell cycle, ribosome, base excision repair, aminoacyl-tRNA biosynthesis, and mismatch repair. For immune checkpoint analysis, we found that PDCD1LG2 and CD226 were expressed at significantly higher levels in patients with metastasis than in those without metastasis. In addition, higher expression of CD226 significantly increased the risk of metastasis (HR: 3.65, 95% CI 1.58–8.42, p = 0.006). We observed that AZD7762, PHA-793887, PI-103, and SNX-2112 might be sensitive to ALDH2 and ALCAM, and PC3 could be the potential cell line used to investigate the interaction among ALDH2, ALCAM, and the above drugs. Conclusions We found that CSGPI might serve as an effective biomarker predicting metastasis probability and radioresistance for PCa and proposed that immune evasion was involved in the process of PCa metastasis.

Background: Bladder cancer (BC) is a common malignancy worldwide that accounts for 3% of global cancer diagnoses. Chemotherapy resistance limits the therapeutic effect of chemotherapeutic agents in patients with BC. Prolyl 4-hydroxylase, beta polypeptide (P4HB) is an endoplasmic reticulum (ER) chaperone that is upregulated in bladder cancer tissues (The Cancer Genome Atlas, TCGA datasets). Knockdown or suppression of P4HB exerts anticancer activity and sensitizes cells to chemotherapy in various types of cancer. Purpose: We aimed to investigate whether the inhibition of P4HB enhances the anticancer efficacy of gemcitabine (GEM) in BC cells and to study the underlying molecular mechanisms. Patients and Methods: The P4HB mRNA expression levels of 411 BC patients from the TCGA database and P4HB expression level of eighty BC paraffin-embedded samples detected by immunohistochemistry (IHC) staining were used for clinical feature and prognostic analyses. Bioinformatics analysis was utilized for the mechanistic investigation. Highly P4HB-expressed BC cell lines (T24 and 5637) treated with P4HB inhibitor (Bacitracin, BAC) were used to study the effects of BAC on the sensitivity of BC cells to GEM and the potential mechanism. P4HB inhibition experiments were performed in highly P4HB-expressed BC cells, and cell viability, colony formation, cell cycle, reactive oxygen species (ROS), apoptosis and pathway proteins were assessed in T24 and 5637 cells. Results: Western blot analysis showed that P4HB expression was significantly higher in BC tissues than in paired normal tissues. IHC showed that patients with high P4HB expression had a poorer overall survival (OS) rate than those with low P4HB expression. Furthermore, increased P4HB expression was demonstrated to be an independent prognostic marker for BC. Functionally, P4HB inhibition by BAC decreased the cell proliferation ability in vitro. Moreover, BAC treatment sensitized BC cells to GEM. Molecular mechanism analysis indicated that inhibition of P4HB by BAC treatment enhanced the anticancer effects of GEM through increasing cellular ROS content and promoting cell apoptosis and PERK/eIF2α/ATF4/CHOP signaling. Conclusion: High P4HB expression was significantly correlated with poor prognosis in BC patients. Inhibition of P4HB by BAC decreased the cell proliferation ability and sensitized BC cells to GEM by activating apoptosis and the PERK/eIF2α/ATF4/CHOP pathways.