Integration of PSAd and multiparametric MRI to forecast biopsy outcomes in biopsy-naïve patients with PSA 4~20 ng/ml.

Introduction: This study aims to investigate whether the transrectal ultrasound-guided combined biopsy (CB) improves the detection rates of prostate cancer (PCa) and clinically significant PCa (csPCa) in biopsy-naïve patients. We also aimed to compare the Prostate Imaging Reporting and Data System (PI-RADS v2.1) score, ADC values, and PSA density (PSAd) in predicting csPCa by the combined prostate biopsy. Methods: This retrospective and single-center study included 389 biopsy-naïve patients with PSA level 4~20 ng/ml, of whom 197 underwent prebiopsy mpMRI of the prostate. The mpMRI-based scores (PI-RADS v2.1 scores and ADC values) and clinical parameters were collected and evaluated by logistic regression analyses. Multivariable models based on the mpMRI-based scores and clinical parameters were developed by the logistic regression analyses to forecast biopsy outcomes of CB in biopsy-naïve patients. The ROC curves measured by the AUC values, calibration plots, and DCA were performed to assess multivariable models. Results: The CB can detect more csPCa compared with TRUSB (32.0% vs. 53%). The Spearman correlation revealed that Gleason scores of the prostate biopsy significantly correlated with PI-RADS scores and ADC values. The multivariate logistic regression confirmed that PI-RADS scores 4, 5, and prostate volume were important predictors of csPCa. The PI-RADS+ADC+PSAd (PAP) model had the highest AUCs of 0.913 for predicting csPCa in biopsy-naïve patients with PSA level 4~20 ng/ml. When the biopsy risk threshold of the PAP model was greater than or equal to 0.10, 51% of patients could avoid an unnecessary biopsy, and only 5% of patients with csPCa were missed. Conclusion: The prebiopsy mpMRI and the combined prostate biopsy have a high CDR of csPCa in biopsy-naïve patients. A multivariable model based on the mpMRI-based scores and PSAd could provide a reference for clinicians in forecasting biopsy outcomes in biopsy-naïve patients with PSA 4~20 ng/ml and make a more comprehensive assessment during the decision-making of the prostate biopsy.

Crosstalk of disulfidptosis-related subtypes identifying a prognostic signature to improve prognosis and immunotherapy responses of clear cell renal cell carcinoma patients.

BACKGROUND: Disulfidptosis is a novel form of programmed cell death induced by high SLC7A11 expression under glucose starvation conditions, unlike other known forms of cell death. However, the roles of disulfidptosis in cancers have yet to be comprehensively well-studied, particularly in ccRCC. METHODS: The expression profiles and somatic mutation of DGs from the TCGA database were investigated. Two DGs clusters were identified by unsupervised consensus clustering analysis, and a disulfidptosis-related prognostic signature (DR score) was constructed. Furthermore, the predictive capacity of the DR score in prognosis was validated by several clinical cohorts. We also developed a nomogram based on the DR score and clinical features. Then, we investigated the differences in the clinicopathological information, TMB, tumor immune landscapes, and biological characteristics between the high- and low-risk groups. We evaluated whether the DR score is a robust tool for predicting immunotherapy response by the TIDE algorithm, immune checkpoint genes, submap analysis, and CheckMate immunotherapy cohort. RESULTS: We identified two DGs clusters with significant differences in prognosis, tumor immune landscapes, and clinical features. The DR score has been demonstrated as an independent risk factor by several clinical cohorts. The high-risk group patients had a more complicated tumor immune microenvironment and suffered from more tumor immune evasion in immunotherapy. Moreover, patients in the low-risk group had better prognosis and response to immunotherapy, particularly in anti-PD1 and anti-CTLA-4 inhibitors, which were verified in the CheckMate immunotherapy cohort. CONCLUSION: The DR score can accurately predict the prognosis and immunotherapy response and assist clinicians in providing a personalized treatment regime for ccRCC patients.

An innovative model based on N7-methylguanosine-related lncRNAs for forecasting prognosis and tumor immune landscape in bladder cancer.

BACKGROUND: As a novel type of the prevalent post-transcriptional modifications, N7-methylguanosine (m7G) modification is essential in the tumorigenesis, progression, and invasion of many cancers, including bladder cancer (BCa). However, the integrated roles of m7G-related lncRNAs in BCa remain undiscovered. This study aims to develop a prognostic model based on the m7G-related lncRNAs and explore its predictive value of the prognosis and anti-cancer treatment sensitivity. METHODS: We obtained RNA-seq data and corresponding clinicopathological information from the TCGA database and collected m7G-related genes from previous studies and GSEA. Based on LASSO and Cox regression analysis, we developed a m7G prognostic model. The Kaplan-Meier (K-M) survival analysis and ROC curves were performed to evaluate the predictive power of the model. Gene set enrichment analysis (GSEA) was conducted to explore the molecular mechanisms behind apparent discrepancies between the low- and high-risk groups. We also investigated immune cell infiltration, TIDE score, TMB, the sensitivity of common chemotherapy drugs, and the response to immunotherapy between the two risk groups. Finally, we validated the expression levels of these ten m7G-related lncRNAs in BCa cell lines by qRT-PCR. RESULTS: We developed a m7G prognostic model (risk score) composed of 10 m7G-related lncRNAs that are significantly associated with the OS of BCa patients. The K-M survival curves revealed that the high-risk group patients had significantly worse OS than those in the low-risk group. The Cox regression analysis confirmed that the risk score was a significant independent prognostic factor for BCa patients. We found that the high-risk group had higher the immune scores and immune cell infiltration. Furthermore, the results of the sensitivity of common anti-BCa drugs showed that the high-risk group was more sensitive to neoadjuvant cisplatin-based chemotherapy and anti-PD1 immunotherapy. Finally, qRT-PCR revealed that AC006058.1, AC073133.2, LINC00677, and LINC01338 were significantly downregulated in BCa cell lines, while the expression levels of AC124312.2 and AL158209.1 were significantly upregulated in BCa cell lines compared with normal cell lines. CONCLUSION: The m7G prognostic model can be applied to accurately predict the prognosis and provide robust directions for clinicians to develop better individual-based and precise treatment strategies for BCa patients.

Partial versus radical nephrectomy for the treatment of pT3aN0M0 renal cell carcinoma: A propensity score analysis.

BACKGROUND: The survival benefit of partial nephrectomy (PN) in pT3a RCC patients is controversial. Here we aimed to explore the potential benefit of PN for pT3aN0M0 renal cell carcinoma (RCC). MATERIAL AND METHODS: Data of patients with pT3aN0M0 RCC who were diagnosed between 2010 and 2012 in the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. Overall survival (OS) and cancer specific survival (CSS) were compared using a Cox proportional hazards model between PN and radical nephrectomy (RN) in pT3aN0M0 RCC. Propensity score (-adjusted, -stratified, -weighted, and -matched) analyses were performed to control for imbalances in individual risk factors. RESULTS: A total of 1277 patients with pT3aN0M0 RCC were identified, of whom 200 patients were treated with PN and 1077 patients were RN. PN showed favorable OS and CSS in 0-4 cm pT3aN0M0 RCC (P < 0.05), and similar OS and CSS in 4-7 cm pT3aN0M0 RCC, compared with RN using un-adjusted analyses. The Propensity score analyses further demonstrated the survival benefit of PN compared with the RN in 0-4 cm pT3aN0M0 RCC (P < 0.05). CONCLUSIONS: In this retrospective study, PN was associated with improved survival compared with RN in 0-4 cm pT3aN0M0 RCC. Moreover, survival was comparable between PN and RN in 4-7 cm pT3aN0M0 RCC. These data provided evidence that PN could be an alternative choice for T3aN0M0 RCC less than 7 cm. Particularly, patients with 0-4 cm pT3aN0M0 RCC might benefit from PN.

A cuproptosis-related LncRNA signature: Integrated analysis associated with biochemical recurrence and immune landscape in prostate cancer.

Background: As a new form of regulated cell death, cuproptosis differs profoundly from apoptosis, ferroptosis, pyroptosis, and necroptosis. The correlation between cuproptosis and long non-coding RNAs (lncRNAs) has been increasingly studied recently. In this study, a novel cuproptosis-related lncRNA prognostic signature was developed to investigate biochemical recurrence (BCR) and tumor immune landscape in prostate cancer (PCa). Methods and Materials: The transcriptome data and clinicopathologic information of PCa patients were downloaded from The Cancer Genome Atlas (TCGA). Pearson's correlation analysis was applied to identify lncRNAs associated with cuproptosis. Based on Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression analysis, we developed a cuproptosis-related lncRNA prognostic model (risk score) to predict the BCR of PCa patients. Additionally, we also constructed a nomogram with the risk score and clinicopathologic features. The biological function, tumor mutation burden (TMB), immune cell infiltration, expression levels of immune checkpoint genes, and anti-cancer drug sensitivity were investigated. Results: We constructed and validated the cuproptosis-related lncRNA signature prognostic model (risk score) by six crlncRNAs. All patients were divided into the low- and high-risk groups based on the median risk score. The Kaplan-Meier (KM) survival analysis revealed that the high-risk group had shorter BCR-free survival (BCRFS). The risk score has been proven to be an independent prognostic factor of BCR in PCa patients. In addition, a nomogram of risk scores and clinicopathologic features was established and demonstrated an excellent predictive capability of BCR. The ROC curves further validated that this nomogram had higher accuracy of predicting the BCR compared to other clinicopathologic features. We also found that the high-risk group had higher TMB levels and more infiltrated immune cells. Furthermore, patients with high TMB in the high-risk group were inclined to have the shortest BCRFS. Finally, patients in the high-risk group were more susceptible to docetaxel, gefitinib, methotrexate, paclitaxel, and vinblastine. Conclusion: The novel crlncRNA signature prognostic model shows a greatly prognostic prediction value of BCR for PCa patients, extends our thought on the association of cuproptosis and PCa, and provides novel insights into individual-based treatment strategies for PCa.

Corrigendum: Label-free LC-MS/MS proteomics analyses reveal CLIC1 as a predictive biomarker for bladder cancer staging and prognosis.

[This corrects the article DOI: 10.3389/fonc.2022.1102392.].

Sex Hormones Had Mediation in the Connection Between Certain Blood Routine Parameters and Bone Loss.

To investigate the association between blood routine (BRT) parameters and bone loss as well as the possible mechanism of this association with bone loss in the middle- aged and elderly patients. A total of nine hundred and ninety-eight subjects (the total) aged≥40 years in General Hospital of Southern Theater Command of People's Liberation Army from March 2015 to January 2018 were enrolled in a cross-sectional studyPatients were divided into two groups as "at least osteopenia group" (including osteopenia, osteoporosis, and severe osteoporosis) and "normal group" according to the diagnosis standard of OP. The above indicators were analyzed and compared between the two groups. Binary multivariate logistic regression analysis was carried out to explore the association between BRT parameters and risk of bone loss in the subjects Mediation Effect was conducted to test endocrine variables as mediators in the correlation of BRT parameters with the bone loss for the possible mechanisms. There were 669 cases in the at least osteopenia group and 329 in the normal group. RBC, Hb, HCT and MCHC were all positively correlated with BMD of lumbar spine(L1-4), left femoral neck and left femur, along with lymph positively correlated with BMD of left femoral neck and left femur, respectively. Eosinophils(Eo) was positively correlated with BMD of L1-L4 and RDW-SD together with RDW-CV were both negatively correlated with BMD of left femoral neck and left femur. By binary multivariate logistic regression, only Hb was associated with bone loss and the OR value was 0.478 as protective factor for BMD. Estradiol (E2) and testosterone (T) had partial mediating effect on the association of BRT parameters with the risk of bone loss. The mediating effect of E2 on the relationship between WBC and bone loss accounted for 46.35% of the total effect, and that of T on the relationship between RBC, Hb, HCT, MCHC and bone loss accounted for 27%, 18.3%, 31.1% and 26.8%, respectively. Bone loss in the middle-aged and elderly population is accompanied with the change of BRT parameters and the erythrocyte indices tend to be more obvious especially the Hb, which indicates anemia had a potential connection with bone loss. Sex hormone, especially T, is an important mediating variable in the association between blood routine parameters and bone loss.

CircME1 promotes aerobic glycolysis and sunitinib resistance of clear cell renal cell carcinoma through cis-regulation of ME1.

Circular RNAs (circRNAs) play critical roles in clear cell renal cell carcinoma (ccRCC). However, their involvement in sunitinib resistance remains largely unknown. Herein, we identified a novel circRNA, named circME1, which contributes to sunitinib resistance development in ccRCC. CircME1 also promoted proliferation, migration, and invasion of ccRCC cells. Further mechanism analysis showed that circME1 interacted with U1 snRNP at the promoter of its parental gene ME1, thereby upregulating the expression of ME1, enhancing aerobic glycolysis of ccRCC, and promoting its malignant phenotype. Furthermore, ME1 specific inhibitor could effectively repress the oncogenic functions of circME1. Taken together, our study demonstrates that the circME1/ME1 pathway is involved in ccRCC progression and sunitinib resistance development, which may be exploited for anticancer therapy.

The impact of tumor size on the survival of patients with small renal masses: A population-based study.

BACKGROUND: Active surveillance (AS) with delayed intervention has gained acceptance as a management strategy for small renal masses (SRMs). However, during AS, there is a risk of tumor growth. Thus, we aim to investigate whether tumor growth in patients with SRMs leads to tumor progress. METHODS: In this study, we enrolled 16,070 patients from the Surveillance, Epidemiology, and End Results database with T1a renal cell carcinoma (RCC) between 2004 and 2017. The 16,070 patients were divided into three groups: 10,526 in the partial nephrectomy (PN) group, 2768 in the local ablation (LA) group, and 2776 in the AS group. Associations of tumor size with all-cause and cancer-specific mortality were evaluated using Kaplan-Meier analyses and Cox regression models. RESULTS: Four tumor size categories were delineated (≤1, >1-2, >2-3, and > 3-4 cm in diameter), and 10-year all-cause and cancer-specific mortality both significantly increased with increasing tumor size in the PN, LA, and AS groups (all p < 0.05). Tumors were substaged based on diameter: T1aA (≤2 cm) and T1aB (>2-4 cm). All-cause and cancer-specific mortality were significantly higher in T1aB tumors than T1aA tumors in each group (hazard ratio = 1.395 and 1.538, respectively; all p < 0.05). CONCLUSIONS: Tumor growth relates to worse prognosis of T1a RCC, and 2 cm serves as a size threshold that is prognostically relevant for patients with T1a RCC. Because of the lack of accurate predictors of tumor growth rate, AS for patients with SRMs incurs a risk of tumor progression.

Label-free LC-MS/MS proteomics analyses reveal CLIC1 as a predictive biomarker for bladder cancer staging and prognosis.

Introduction: Bladder cancer (BC) is a significant carcinoma of the urinary system that has a high incidence of morbidity and death owing to the challenges in accurately identifying people with early-stage BC and the lack of effective treatment options for those with advanced BC. Thus, there is a need to define new markers of prognosis and prediction. Methods: In this study, we have performed a comprehensive proteomics experiment by label-free quantitative proteomics to compare the proteome changes in the serum of normal people and bladder cancer patients-the successful quantification of 2064 Quantifiable proteins in total. A quantitative analysis was conducted to determine the extent of changes in protein species' relative intensity and reproducibility. There were 43 upregulated proteins and 36 downregulated proteins discovered in non-muscle invasive bladder cancer and normal individuals. Sixty-four of these proteins were elevated, and 51 were downregulated in muscle-invasive and non-muscle-invasive bladder cancer, respectively. Functional roles of differentially expressed proteins were annotated using Gene Ontology (GO) and Clusters of Orthologous Groups of Proteins (COG). To analyze the functions and pathways enriched by differentially expressed proteins, GO enrichment analysis, protein domain analysis, and KEGG pathway analysis were performed. The proteome differences were examined and visualized using radar plots, heat maps, bubble plots, and Venn diagrams. Results: As a result of combining the Venn diagram with protein-protein interactions (PPIs), Chloride intracellular channel 1 (CLIC1) was identified as the primary protein. Using the Gene Set Cancer Analysis (GSCA) website, the influence of CLIC1 on immune infiltration was analyzed. A negative correlation between CD8 naive and CLIC1 levels was found. For validation, immunohistochemical (IHC), qPCR, and western blotting (WB) were performed.Further, we found that CLIC1 was associated with a poor prognosis of bladder cancer in survival analysis. Discussion: Our research screened CLIC1 as a tumor-promoting protein in bladder cancer for the first time using serum mass spectrometry. And CLIC1 associated with tumor stage, and immune infiltrate. The prognostic biomarker and therapeutic target CLIC1 may be new for bladder cancer patients.

LncRNA nuclear-enriched abundant transcript 1 shuttled by prostate cancer cells-secreted exosomes initiates osteoblastic phenotypes in the bone metastatic microenvironment via miR-205-5p/runt-related transcription factor 2/splicing factor proline- and glutamine-rich/polypyrimidine tract-binding protein 2 axis.

Prostate cancer (PCa) patients commonly present with osteoblastic-type bone metastasis. Exosomes derived from tumor cells possess biological significance and can mediate intercellular communication in the tumor microenvironment. Long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) is also implicated in the stability in tumorigenesis and the development of PCa, but the underlying mechanism remains elusive. Hence, the current study set out to investigate the physiological mechanisms by which exosomes-encapsulated NEAT1 affects the progression of PCa. First, after isolation, we found PCa cell-derived exosomes induced the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Besides, NEAT1 in PCa cells could be transferred into hBMSCs via exosomes. Further gain- and loss-of-function experimentation revealed that NEAT1 acted as a competing endogenous RNA (ceRNA) of microRNA (miR)-205-5p to upregulate the runt-related transcription factor 2 (RUNX2) levels. Moreover, NEAT1 could promote the RUNX2 expression via the splicing factor proline- and glutamine-rich (SFPQ)/polypyrimidine tract-binding protein 2 (PTBP2) axis. Functional assays uncovered that NEAT1 shuttled by PCa-exosomes facilitated the activity of alkaline phosphatase (ALP) and mineralization of extracellular matrix, and continuously upregulated the levels of RUNX2, ALP, alpha-1 type 1 collagen, and osteocalcin by regulating RUNX2, to induce the osteogenic differentiation of hBMSCs. Furthermore, in vivo experimentation confirmed that upregulated NEAT1 induced osteogenesis. Collectively, our findings indicated that PCa-derived exosomes-loaded NEAT1 upregulated RUNX2 to facilitate the osteogenesis of hBMSCs by competitively binding to miR-205-5p via the SFPQ/PTBP2 axis, therefore providing a potential therapeutic target to treat osteogenesis of hBMSCs in PCa. PCa cells secrete exosomes containing NEAT1, and NEAT1 exerts effects on osteogenic differentiation of hBMSCs in PCa. NEAT1 shuttled by PCa-derived exosomes could be transferred into hBMSCs, where NEAT1 exerted inductive properties in osteogenic differentiation of hBMSCs through the upregulation of RUNX2 by competitively binding to miR-205-5p and regulating SFPQ/PTBP2 in vitro and in vivo.

Intra-arterial chemotherapy combined with intravesical chemotherapy compared with intravesical BCG immunotherapy retrospectively in high-risk non-muscle-invasive bladder cancer after transurethral resection of the bladder tumor.

OBJECTIVE: To compare the efficacy and safety of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IVC) against intravesical BCG immunotherapy in high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of the bladder tumor (TURBT). MATERIALS AND METHODS: 130 patients with high-risk NMIBC who had underwent TURBT were divided into two groups, of which IAC + IVC group received four courses of IAC (cisplatin and epirubicin) combined with IVC (epirubicin or pirarubicin) after surgery and BCG group received intravesical BCG immunotherapy. Recurrence rate and progression rate were assessed by Chi-square test, while recurrence-free survival and progression-free survival were calculated using the Kaplan-Meier method. RESULTS: In this study, the recurrence rate was 27.9% (12/43) in IAC + IVC group and 26.4% (14/53) in BCG group, while progression rate was 9.3% (4/43) in IAC + IVC group and 9.4% (5/53) in BCG group. Both of the recurrence and progression rate did not show a significant difference. In the Kaplan-Meier plot, no difference was found with respect to recurrence-free survival and progression-free survival. Moreover, 46.5% (20/43) patients suffered from adverse events of IAC and 83.1% (49/59) patients suffered from adverse events associated with BCG, of which 6 patients discontinued treatment due to serious adverse events of BCG. Univariate analysis suggested that only recurrent tumor could be an independent risk factor related to recurrence. CONCLUSIONS: IAC combined with IVC used in high-risk NMIBC could reduce the recurrence and progression as effective as BCG instillation with lower adverse events.

Comparison of T2N0M0 and T3aN0M0 in Predicting the Prognosis of Patients With Renal Cell Carcinoma.

Background: To investigate the prognostic role of tumor size in patients with pathological T2N0M0 and T3aN0M0 renal cell carcinoma (RCC) treated by radical surgery. Methods: A total of 3,662 cases were retrospectively analyzed from the Surveillance, Epidemiology and End Results (SEER) from 2010 to 2012. Overall survival (OS) and cancer-specific survival (CSS) data were obtained. The log-rank test was used to compare survival distributions and Cox proportional hazards model was used for univariate and multivariate analyses, respectively. Results: In the low-risk T3aN0M0 (perinephric fatty infiltration or sinus fatty infiltration only) group, patients with tumor size ≤ 7 cm were associated with a better OS (P = 0.009) and CSS (P < 0.001) than those with tumor size >7 cm. However, there was no difference in OS (P = 0.129) and CSS (P = 0.539) between T2bN0M0 patients and low-risk T3aN0M0 patients with tumor size ≤ 7 cm. A new T classification grouping patients with both T2bN0M0 and T3aN0M0 with tumor diameter ≤ 7 cm into the same staging category (pT2aN0M0, pT2bN0M0+low-risk pT3aN0M0 [tumor diameter ≤ 7cm], low-risk pT3aN0M0 [tumor diameter >7 cm], high-risk pT3aN0M0) was proposed and it was found as an independent predictive variable for OS and CSS. Conclusions: Findings from the present study suggest that the reclassification of pT2N0M0 and pT3aN0M0 RCC can lead to better prediction of OS and CSS.

Human bone marrow mesenchymal stem cells-derived microRNA-205-containing exosomes impede the progression of prostate cancer through suppression of RHPN2.

BACKGROUND: Human bone marrow mesenchymal stem cells (hBMSCs) are implicated in cancer initiation and metastasis, sometimes by releasing exosomes that mediate cell communication by delivering microRNAs (miRNAs). This study aimed to investigate the physiological mechanisms by which exosomal miR-205 derived from hBMSCs may modulate the growth of prostate cancer cells. METHODS: Microarray-based gene expression profiling of prostate cancer was adopted to identify differentially expressed genes and regulatory miRNAs, which identified the candidates RHPN2 and miR-205 as the study focus. Then the binding affinity between miR-205 and RHPN2 was identified using in silico analysis and luciferase activity detection. Prostate cancer cells were co-cultured with exosomes derived from hBMSCs treated with either miR-205 mimic or miR-205 inhibitor. Subsequently, prostate cancer cell proliferation, invasion, migration, and apoptosis were detected in vitro. The effects of hBMSCs-miR-205 on tumor growth were investigated in vivo. RESULTS: miR-205 was downregulated, while RHPN2 was upregulated in prostate cancer cells. RHPN2 was a target of miR-205, and upregulated miR-205 inhibited prostate cancer cell proliferation, invasion, and migration and promoted apoptosis by targeting RHPN2. Next, experiments demonstrated that hBMSCs-derived exosomes carrying miR-205 contributed to repressed prostate cancer cell proliferation, invasion, and migration and enhanced apoptosis. Furthermore, in vivo assays confirmed the inhibitory effects of hBMSCs-derived exosomal miR-205 on prostate cancer. CONCLUSION: The hBMSCs-derived exosomal miR-205 retards prostate cancer progression by inhibiting RHPN2, suggesting that miR-205 may present a predictor and potential therapeutic target for prostate cancer.

Auxiliary diagnostic value of p16 amplification combined with the detection of heterozygous and homozygous loss for urothelial carcinoma.

The present study aimed to investigate the significance of detecting cyclin dependent kinase inhibitor 2A (p16) gene aberrations in the diagnosis of urothelial carcinoma (UC) using fluorescence in situ hybridization (FISH). A total of 77 voided urine specimens from 65 patients with UC and 12 patients with benign urinary disease were recruited into the current study. Under a fluorescence microscope, cells with large and irregular nuclei were assessed for chromosomal aberrations. The positive rate of p16 amplification in UC samples was 32.3% (21/65), which was significantly higher than that in benign urinary disease samples (16.7%, 2/12; P<0.05). Heterozygous and homozygous loss of p16 was identified in 12 (18.5%) and 23 (35.4%) patients with UC, respectively; p16 expression in the remainder of patients was normal. In addition, as tumor stage or grade advanced, the positive rate of p16 aberrations also increased significantly (P<0.05). In conclusion, p16 gene aberrations may serve important roles in the auxiliary diagnosis of UC by FISH and could be utilized to monitor UC progression.

Vasculogenic mimicry in bladder cancer and its association with the aberrant expression of ZEB1.

The aim of the present study was to investigate the associations between vasculogenic mimicry (VM) and zinc finger E-box binding homeobox 1 (ZEB1) in bladder cancer. VM structure and ZEB1 expression were analyzed by cluster of differentiation 34/periodic acid Schiff (PAS) double staining and immunohistochemical staining in 135 specimens from patients with bladder cancer, and a further 12 specimens from normal bladder tissues. Three-dimensional (3-D) culture was used to detect VM formation in the bladder transitional cancer cell lines UM-UC-3 and J82, and the immortalized human bladder epithelium cell line SV-HUC-1 in vitro. ZEB1 expression in these cell lines was compared by reverse transcription-quantitative polymerase chain reaction and western blot assays. In addition, small interfering RNA was used to inhibit ZEB1 in UM-UC-3 and J82 cells, followed by 3-D culturing of treated cell lines. As a result, VM was observed in 31.1% of specimens from bladder cancer tissues, and cases with high ZEB1 expression accounted for 60.0% of patients with bladder cancer. In addition, ZEB1 expression was closely associated with VM (r=0.189; P<0.05), and also increased as the grade and stage of the tumor developed. In an in vitro assay, UM-UC-3 and J82 cells exhibited VM formation, however, SV-HUC-1 did not. Furthermore, VM-forming cancer cell lines UM-UC-3 and J82 exhibited higher ZEB1 expression. Notably, VM formation was inhibited following knockdown of ZEB1. In conclusion, ZEB1 may be associated with VM in bladder cancer and serve an important role in the process of VM formation. However, its detailed mechanism requires further study.

En bloc transurethral resection with 2-micron continuous-wave laser for primary non-muscle-invasive bladder cancer: a randomized controlled trial.

PURPOSE: To evaluate the practicability of en bloc transurethral resection with 2-micron continuous-wave laser as treatment for primary non-muscle-invasive bladder cancer (NMIBC). METHODS: This was a single-center, randomized, controlled trial involving 142 patients with newly diagnosed NMIBC. All patients were randomly assigned in a 1:1 ratio to receive either laser treatment or conventional transurethral resection of bladder tumor (TURBT). All patients received intravesical chemotherapy. Follow-up was performed in 18 months. Primary outcome measure was difference of tumor recurrence rate at the end of study. RESULTS: Baseline characteristics did not differ between patients in two groups. Operation time was longer in laser group than in TURBT group (56.5 ± 37.4 vs. 41.0 ± 29.4 min, P = 0.017). Obturator nerve reflection was noted during TURBT in 18 patients, whereas none was noted during laser resection. Number of T1 tumors was higher in the laser group (25 vs. 15, P = 0.047). According to Kaplan-Meier survival curves, there was no statistical difference in the rate of recurrence in 18 months (P = 0.383). All recurrences were out of the site of first resection, and there was no progression in tumor grade. CONCLUSION: Two-micron continuous-wave laser did not diminish tumor recurrence rate in primary NMIBC for 18-months observation. However, T1 tumors were significantly higher among laser group. Clear and complete tumor bases were easily conserved by laser resection, which may enable pathologists to distinguish the T stages of bladder cancer more easily. Further studies need to be done in future.

The performance of transrectal ultrasound in the diagnosis of seminal vesicle defects: a comparison with magnetic resonance imaging.

Obstructive azoospermia (OA) is one of the most common causes of male infertility. Transrectal ultrasound (TRUS) has been used to diagnose OA for many years. From 2009 to 2013, we evaluated a prospective cohort of 1249 patients with suspected OA using TRUS. It was found that dilation of the ejaculatory duct (ED) (29.9%, 374/1249) was the most common cause of OA, followed by seminal vesicle (SV) abnormalities (28.5%, 356/1249). A total of 237 patients were diagnosed with congenital defects (agenesis and/or hypoplasia) of the SV, constituting more than half of the cases of SV disease in OA (19.0%, 237/1249). In contrast to ED, congenital defects of the SV could not be corrected with surgical treatment. Therefore, it is meaningful to compare TRUS and magnetic resonance imaging (MRI) for accurate diagnosis of SV defects. Among our patients, 30 with agenesis or/and hypoplasia of the SV on TRUS were further evaluated using pelvic MRI within 2 years, with the objective of verifying the TRUS results. The concordance rate for diagnosing congenital defects of the SV was 73.3% (22/30). We concluded that TRUS is a reliable and convenient method for diagnosing agenesis or hypoplasia of the SV in OA patients with a high concordance with MRI while MRI is useful in patients with inconclusive TRUS findings.