A preoperative magnetic resonance imaging-based model to predict biochemical failure after radical prostatectomy.

To investigate if a magnetic resonance imaging (MRI)-based model reduced postoperative biochemical failure (BF) incidence in patients with prostate cancer (PCa). From June 2018 to January 2020, we retrospectively analyzed 967 patients who underwent prostate bi-parametric MRI and radical prostatectomy (RP). After inclusion criteria were applied, 446 patients were randomized into research (n = 335) and validation cohorts (n = 111) at a 3:1 ratio. In addition to clinical variables, MRI models also included MRI parameters. The area under the curve (AUC) of receiver operating characteristic and decision curves were analyzed. The risk of postoperative BF, defined as persistently high or re-elevated prostate serum antigen (PSA) levels in patients with PCa with no clinical recurrence. In the research (age 69 [63-74] years) and validation cohorts (age 69 [64-74] years), the postoperative BF incidence was 22.39% and 27.02%, respectively. In the research cohort, the AUC of baseline and MRI models was 0.780 and 0.857, respectively, with a significant difference (P < 0.05). Validation cohort results were consistent (0.753 vs. 0.865, P < 0.05). At a 20% risk threshold, the false positive rate in the MRI model was lower when compared with the baseline model (31% [95% confidence interval (CI): 9-39%] vs. 44% [95% CI: 15-64%]), with the true positive rate only decreasing by a little (83% [95% CI: 63-94%] vs. 87% [95% CI: 75-100%]). 32 of 100 RPs can been performed, with no raise in quantity of patients with missed BF. We developed and verified a MRI-based model to predict BF incidence in patients after RP using preoperative clinical and MRI-related variables. This model could be used in clinical settings.

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Inhibit Triple-Negative Breast Cancer Cell Stemness and Metastasis via an ALKBH5-Dependent Mechanism.

BACKGROUND: Abnormal N6-methyladenosine (m6A) modification caused by m6A regulators is a common characteristic in various tumors. However, little is known about the role of m6A regulator AlkB homolog 5 (ALKBH5) in triple-negative breast cancer (TNBC). In this study, we analyzed the influence of ALKBH5 on the stemness of TNBC and the molecular mechanism using bioinformatics analysis and in vivo animal experiments. METHODS: RNA expression data and single-cell RNA sequencing (scRNA-seq) data were downloaded from the TCGA and GEO databases. Following intersection analysis, key genes involved in the TNBC cell stemness were determined, which was followed by functional enrichment analysis, PPI and survival analysis. Exosomes were extracted from bone marrow mesenchymal stem cells (BMSC-Exos) where ALKBH5 inhibition assay was conducted to verify their function in the biological characteristics of TNBC cells. RESULTS: Bioinformatics analysis revealed 45 key genes of ALKBH5 regulating TNBC cell stemness. In addition, UBE2C was predicted as a key downstream gene and p53 was predicted as a downstream signaling of ALKBH5. In vivo data confirmed that ALKBH5 upregulated UBE2C expression by regulating the m6A modification of UBE2C and reduced p53 expression, thus promoting the stemness, growth and metastasis of TNBC cells. BMSC-Exos suppressed the tumor stemness, growth and metastasis of TNBC cells and ALKBH5 shRNA-loaded BMSC-Exos showed a more significant suppressive role. CONCLUSION: Taken together, our findings indicated that ALKBH5 shRNA-loaded BMSC-Exos reduced TNBC cell stemness, growth and metastasis and define a promising strategy to treat TNBC.

A comprehensive prostate biopsy standardization system according to quantitative multiparametric MRI and PSA value: P.R.O.S.T score.

BACKGROUND: Although most studies believe that systematic biopsy (SB) and targeted biopsy (TB) should be performed simultaneously in patients with suspected prostate cancer, we believe that patients with the Prostate Imaging-Reporting and Data System (PI-RADS) score of 4/5 may be able to perform TB only. METHODS: We retrospectively analyzed the pathological results of patients undergoing transperineal prostate biopsy with PI-RADS 4 and 5 in our center. We use the data from 2019 to 2020 as the training set to establish the prediction model and the data from 2021 as the verification set to test the effectiveness. Through stepwise logistics regression analysis, we integrate statistically significant clinical factors and establish a model to further predict whether the target area is tumor. RESULTS: The results showed that age (O), total number of lesions (T), histological region (R), PI-RADS score (S), and PSA density (P) were significantly correlated with the results of TB, and the formula was: p = 1/[1 + e^(- 11.387 + 0.058 × O + (- 0.736 × T) + 0.587 × R + 1.574 × S + 7.338 × P)]. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the prediction model was 0.840 (95% CI 0.802-0.877), with the optimal threshold of 0.762. And the corresponding specificity and sensitivity were 0.765 and 0.752. In the validation set, the AUC of the prediction model was 0.816 (95% CI 0.759-0.874), which means that it has good prediction efficiency. CONCLUSION: The P.R.O.S.T score can effectively screen PI-RADS 4/5 lesions, which may help physicians shunt patients who need prostate biopsy to reduce unnecessary systematic biopsies.

[Long intergenic non-coding RNA 01121 promotes metastasis of prostate cancer cells by activating the EMT process].

OBJECTIVE: To investigate the expression, biological function and potential mechanism of long intergenic non-coding RNA 01121 (LINC01121) in PCa. METHODS: Using real-time quantitative polymerase chain reaction (qRT-PCR), we detected the expression of LINC01121 in PCa cell lines and the efficiency of small interfering RNA (siRNA) in knocking down LINC01121. We examined the biological function of LIC01121 in the PCa cells by CCK8, cell cloning, and Transwell migration and invasion assays, and determined the expressions of epithelial-mesenchymal transition (EMT)-related proteins in the PCa cells by Western blot. RESULTS: The relative expression of LINC01121 was significantly higher in the PCa than in the WPMY1 human normal prostate matrix immortalized cells (P < 0.05). Knocking down the expression of LINC01121 significantly reduced the proliferation, cloning, migration and invasiveness of the PCa cells (P < 0.05), down-regulated the expressions of the N-cadherin and vimentin proteins and up-regulated that of E-cadherin in the PCa cells (P < 0.05). CONCLUSION: LINC01121 is overexpressed in PCa cell lines, which may promote the proliferation, migration and invasiveness of the cells by activating the EMT process.

Use of Prostate Systematic and Targeted Biopsy on the Basis of Bi-Parametric Magnetic Resonance Imaging in Biopsy-Naïve Patients.

OBJECTIVES: To explore the performance of targeted biopsy (TB) in combination with systematic biopsy (SB) in the detection of prostate cancer (PCa) in biopsy naïve patients. METHODS: From May 2018 to January 2020, 230 biopsy-naïve men with suspicious bi-parametric MRI [bpMRI; Prostate Imaging Reporting and Data System (PI-RADS) score ≥3] were enrolled. All patients had prostate-specific antigen (PSA) levels of 20 ng/ml or less. For each patient, transrectal ultrasound-guided prostate biopsy was performed. The primary endpoint was the detection rate of CSPC [clinically-significant PCa, International Society of Urological Pathology grade group (ISUP GG) 2 or higher tumors]. The secondary endpoints were the detection rates of CIPC (clinically insignificant PCa, ISUP GG 1 tumors). RESULTS: CSPC was detected in 90 patients. Twelve (13.33%) of them were detected by TB only and 18 (20.00%) by SB only. Detection of CSPC by SB and TB did not differ significantly (p = .36). In 4.35% of 230 patients, CSPC would have been missed if we performed SB only, and in 6.09% of patients if we performed TB only. Moreover, combination of TB and SB did not increase the detection of CIPC. CONCLUSIONS: No significant difference was found in the detection of CSPC between TB and SB; however, both techniques revealed substantial added value and combination of TB and SB could further improve this detection rate without increasing the detection of CIPC.

Long non-coding RNA profile study identifies an immune-related lncRNA prognostic signature for prostate adenocarcinoma.

Prostate adenocarcinoma (PRAD) is the highest incidence rate of male urogenital morbidity worldwide. Long non-coding RNAs (lncRNAs), as a significant class of gene expression regulators, play a critical role in immune regulation. The purpose of this study is to explore a new immune related lncRNA signature to exactly predict the prognosis of PRAD patients. In this study, we conducted a genome-wide comparative analysis of lncRNA expression profiles in 532 patients with PRAD from the Cancer Genome Atlas (TCGA) database. The immune-related lncRNAs were identified by Cox regression model, and then a new five immune-related lncRNAs signature (FRMD6-AS2, AC008770.3, AC109460.3, AC011899.2, and AC008063.1) were constructed, which could predict the prognosis of PRAD patients. Univariate and multivariate Cox regression analysis showed that the signature could be an independent prognostic indicator of overall survival (OS). Through further study of different clinic-pathological parameters, we found that PRAD samples can be divided into high-risk groups with shorter OS and low-risk groups with longer OS by the signature. Principal component analysis showed that five immune-related lncRNA signature could distinguish the high-risk group from low-risk group in view of the immune-related lncRNAs. The difference of immune status between the two groups was observed by gene set enrichment analysis and the ESTIMATE algorithm. Except FRMD6-AS2, the expression of the other 4 lncRNAs were remarkably up-regulated in tumor tissues. In conclusion, the identified five immune-related lncRNAs signature had important clinical significance in prognosis prediction, and can be used as potential immunotherapy targets for PRAD patients.

Comfortable suture angle with optimized trocar position aids renorrhaphy during retroperitoneal laparoscopic partial nephrectomy.

BACKGROUND: This study investigated a comfortable suture angle (CSA) with optimized trocar position for closing the defect during renorrhaphy in retroperitoneal laparoscopic partial nephrectomy (LPN). The feasibility, usefulness, and safety of achieving the CSA with modified trocar position were determined for different tumor types. METHODS: Two optimized trocar positions were introduced for different tumor types. A suture angle was based on the tumor plane of the superficial parenchyma defect and the line formed by the needle holder. Preliminary surgical simulations determined a CSA that combined the least suture time with the greatest ease of performance. Achieving the CSA was attempted during renorrhaphy of 106 enrolled patients undergoing retroperitoneal LPN. Patients' characteristics, operative features, and follow-up information were collected and analyzed. RESULTS: For 89 (83.96%) patients, a CSA was successfully reached and parenchyma recovered. The remaining 17 patients were successfully sutured, but the attempt to achieve a CSA failed. For the CSA group, the suture, clamping, and overall operative times were significantly less than that of the non-CSA patients. The groups were similar regarding estimated blood loss, positive surgical margin, and rates of glomerular filtration reduction and complications. Univariable analyses determined that tumor location, growth pattern, and R.E.N.A.L. nephrometry score (RNS) may influence the success of this approach. Multivariable analyses indicated that only tumor location and RNS were independent factors affecting successful achievement of the CSA. CONCLUSIONS: Through different kidney position changes, the CSA could be used to ease the suture process. It is feasible and safe to perform a CSA with optimized trocar position during LPN. Tumor location and RNS may influence the approach to get a CSA.

Analysis of risk factors for determining the need for prostate biopsy in patients with negative MRI.

To analyze the clinical characteristics of patients with negative biparametric magnetic resonance imaging (bpMRI) who didn't need prostate biopsies (PBs). A total of 1,012 male patients who underwent PBs in the First Affiliated Hospital of Nanjing Medical University from March 2018 to November 2019, of 225 had prebiopsy negative bpMRI (defined as Prostate Imaging Reporting and Data System (PI-RADS 2.1) score less than 3). The detection efficiency of clinically significant prostate cancer (CSPCa) was assessed according to age, digital rectal examination (DRE), prostate volume (PV) on bpMRI, prostate-specific antigen (PSA) and PSA density (PSAD). The definition of CSPCa for Gleason score > 6. Univariate and multivariable logistic regression analysis were used to identify predictive factors of absent CSPCa on PBs. Moreover, absent CSPCa contained clinically insignificant prostate cancer (CIPCa) and benign result. The detection rates of present prostate cancer (PCa) and CSPCa were 27.11% and 16.44%, respectively. Patients who were diagnosed as CSPCa had an older age (P < 0.001), suspicious DRE (P < 0.001), a smaller PV (P < 0.001), higher PSA value (P = 0.008) and higher PSAD (P < 0.001) compared to the CIPCa group and benign result group. PSAD < 0.15 ng/ml/cm3 (P = 0.004) and suspicious DRE (P < 0.001) were independent predictors of absent CSPCa on BPs. The negative forecast value of bpMRI for BP detection of CSPCa increased with decreasing PSAD, mainly in patients with naive PB (P < 0.001) but not in prior negative PB patients. 25.33% of the men had the combination of negative bpMRI, PSAD < 0.15 ng/ml/cm3 and PB naive, and none had CSPCa on repeat PBs. The incidence of PB was determined, CSPCa was 1.59%, 0% and 16.67% in patients with negative bpMRI and PSAD < 0.15 ng/ml/cm3, patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and biopsy naive and patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and prior negative PB, separately. We found that a part of patients with negative bpMRI, a younger age, no suspicious DRE and PSAD < 0.15 ng/ml/cm3 may securely avoid PBs. Conversely PB should be considered in patients regardless of negative bpMRI, especially who with a greater age, obviously suspicious DRE, significantly increased PSA value, a significantly small PV on MRI and PSAD > 0.15 ng/ml/cm3.

Genetic variants in the cholesterol biosynthesis pathway genes and risk of prostate cancer.

Previous studies have found the relationship between cholesterol biosynthesis pathway genes and the risk or prognosis of prostate cancer (PCa), while there is no definite evidence that genetic variants in the cholesterol biosynthesis pathway gene is related to PCa risk. Consequently, we performed this study to explore the associations of single-nucleotide polymorphisms (SNPs) in the cholesterol biosynthesis pathway with PCa risk. We systematically evaluated the association of SNPs in 21 cholesterol biosynthesis pathway genes with the risk of PCa using the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial database using a logistic regression model. Gene expression data of PCa from Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA) database were applied for mRNA expression analysis. The TCGA database was used to perform expression quantitative trait loci (eQTL) analysis. The interaction between demographic factors and SNPs was analyzed using two-by-four tables. We found T allele of rs67415672 in HMGCS1 is a significant protective allele of PCa [adjusted odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.83-0.97, P = 4.16 × 10-3]. Moreover, rs67415672 was an eQTL for HMGCS1 (P = 2.23 × 10-6). The expression of HMGCS1 significantly decreased in PCa primary tumors than that in normal tissues. These findings indicated that the HMGCS1 rs67415672 might be possible functional susceptibility loci for PCa.

How to Pick Out the "Unreal" Gleason 3 + 3 Patients: A Nomogram for More Precise Active Surveillance Protocol in Low-Risk Prostate Cancer in a Chinese Population.

OBJECTIVE: To develop a nomogram for selecting the "unreal" Gleason score (GS) 3 + 3 patients in biopsy GS 3 + 3 prostate cancer (PCa) patients. METHODS: Patients who were newly diagnosed with PCa by biopsy and underwent radical prostatectomy in the First Affiliated Hospital of Nanjing Medical University from January 2009 to October 2018 were enrolled. Comparisons were made between GS 3 + 3 and higher grade PCa patients. Logistic regression analysis was performed to determine the risk factors for the "unreal" GS 3 + 3 PCa in biopsy GS 3 + 3 patients. Then, a nomogram was developed to predict the probability of "unreal" GS 3 + 3 PCa according to the results of multivariate analysis. Finally, receiver operating characteristic and decision curve analysis (DCA) curves were structured to identify the efficiency of the predictive model. RESULTS: Compared to higher GS grade, biopsy GS 3 + 3 had greater upgrade risk (P < 0.05) while a lower proportion of positive surgical margins, seminal vesicle invasion, extra-prostatic extension, lymph node invasion, and nerve invasion (all P < 0.05). Multivariate analysis showed that age, PSAD, prostate imaging reporting and data system (PI-RADS) score and biopsy positive cores were significant risk factors for "unreal" GS 3 + 3. A nomogram was developed utilizing these factors with high prediction performance (area under curve = 0.924). Furthermore, DCA curve suggested that this predictive model was effective. CONCLUSIONS: The nomogram identified the probability of "unreal" GS 3 + 3 PCa in biopsy GS 3 + 3 PCa patients, which was of great value for clinical guidance in low risk PCa therapy.

Association study between genetic variants in retinol metabolism pathway genes and prostate cancer risk.

BACKGROUND: Evidence suggests that serum retinol level is associated with prostate cancer risk, but the association between genetic variants in the retinol metabolism pathway genes and prostate cancer risk remains unclarified. METHODS: Single-nucleotide polymorphisms (SNPs) in 31 genes in the retinol metabolism pathway were genotyped to evaluate the association with prostate cancer risk in 4,662 cases and 3,114 controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The gene expression analysis was evaluated using data from the Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA) database. Data from the Genotype-Tissue Expression (GTEx) project dataset were utilized to perform the expression quantitative trait loci (eQTL) analysis. RESULTS: Two SNPs were significantly associated with prostate cancer risk [rs1330286 in ALDH1A1: odds ratio (OR) = 0.88, 95% confidence interval (CI) = 0.83-0.94, p = 2.45 × 10-4 ; rs4646653 in ALDH1A3: OR = 1.17, 95% CI =1.07-1.27, p = 4.33 × 10-4 ]. Moreover, the mRNA level of ALDH1A3 was significantly higher in prostate cancer tissues than in normal tissues in both TCGA datasets and GEO datasets (p = 1.63 × 10-12 and p = 4.33 × 10-2 , respectively). rs1330286 was an eQTL of ALDH1A1 (P = 2.90 × 10-3 ). CONCLUSION: Our findings highlight that genetic variants in retinol metabolism pathway genes are associated with prostate cancer risk.

A Comparative Study of Prostate Cancer Detection Rate Between Transperineal COG-TB and Transperineal FUS-TB in Patients with PSA ≤20 ng/mL.

Background: The combination of prebiopsy MRI and transperineal targeted biopsies is being increasingly used to obtain tissues from patients with suspected prostate cancer (PCa). Objective: To investigate the difference in PCa detection rate between transperineal cognitive fusion TB (COG-TB) and transperineal software fusion TB (FUS-TB). Participants: The present study included 163 male patients with suspected PCa who had not undergone prostate biopsy, had a prostate-specific antigen (PSA) level of ≤20 ng/mL, and had been examined by bi-parameter MRI and confirmed to have prostate nodules by prostate imaging reporting and data system version 2 (PI-RADS V2) scores ≥3 (from December 3, 2018 to October 7, 2019). Intervention: Seventy-one patients underwent transperineal COG-TB, and 92 patients underwent transperineal FUS-TB. The detection rate of the first four needles was compared. Results: No significant difference was found in the overall detection rate of PCa between COG-TB and FUS-TB (60.56% vs 51.08%, p = 0.228). This result was consistent even after stratifying by PI-RADS score. There was also no significant difference between COG-TB and FUS-TB in the detection rate of clinically significant PCa (p = 0.641). Moreover, COG-TB and FUS-TB showed no difference in the detection rate of PCa with different Gleason scores. Conclusions: In patients with suspected PCa with PSA ≤20 ng/mL and PI-RADS ≥3, FUS-TB was comparable to COG-TB in the detection rate of PCa.

MiR-129-5p promotes docetaxel resistance in prostate cancer by down-regulating CAMK2N1 expression.

This study focuses on the effect of miR-129-5p on docetaxel-resistant (DR) prostate cancer (PCa) cells invasion, migration and apoptosis. In our study, the expression of CAMK2N1 was assessed by qRT-PCR in PCa patient tissues and cell lines including PC-3 and PC-3-DR. Cells transfected with miR-129-5p mimics, inhibitor, CAMK2N1 or negative controls (NC) were used to interrogate their effects on DR cell invasions, migrations and apoptosis during docetaxel (DTX) treatments. The apoptosis rate of the PCa cells was validated by flow cytometry. Relationships between miR-129-5p and CAMK2N1 levels were identified by qRT-PCR and dual-luciferase reporter assay. CAMK2N1 was found to be down-expressed in DR PCa tissue sample, and low levels of CAMK2N1 were correlated with high docetaxel resistance and clinical prediction of poor survival. CAMK2N1 levels were decreased in DR PCa cells treated with DXT. We further explored that up-regulation of miR-129-5p could promote DR PCa cells viability, invasion and migration but demote apoptosis. Involved molecular mechanism studies revealed that miR-129-5p reduced downstream CAMK2N1 expression to further impact on chemoresistance to docetaxel of PCa cells, indicating its vital role in PCa docetaxel resistance. Our findings revealed that miR-129-5p contributed to the resistance of PC-3-DR cells to docetaxel through suppressing CAMK2N1 expression, and thus targeting miR-129-5p may provide a novel therapeutic approach in sensitizing PCa to future docetaxel treatment.

Exosomal MicroRNA-9-3p Secreted from BMSCs Downregulates ESM1 to Suppress the Development of Bladder Cancer.

Exosomes, carriers to transfer endogenous molecules, derived from bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to play a role in the progression of bladder cancer. Here we aimed to test the functional mechanism of microRNA-9-3p (miR-9-3p)-containing exosomes derived from BMSCs in bladder cancer. BMSCs were cocultured with bladder cancer cells, and exosomes secreted from BMSCs were identified. Next, the expression of miR-9-3p and endothelial cell-specific molecule 1 (ESM1) in bladder cancer tissues and cells was determined. Then effects of miR-9-3p and ESM1 via BMSC-derived exosomes on bladder cancer cell viability, migration, invasion, and apoptosis were determined by loss- and gain-of-function experiments and on in vivo tumor growth, and metastasis was assessed in nude mice. miR-9-3p expression was decreased and ESM1 was increased in bladder cancer. BMSCs inhibited bladder cancer cell viability, migration, and invasion, and induced apoptosis, whereas the addition of exosome secretion inhibitor GW4869 achieved the opposite effects. Moreover, exosomal miR-9-3p upregulation or ESM1 silencing suppressed bladder cancer cell viability, migration, and invasion; induced cell apoptosis; and inhibited in vivo tumor growth and metastasis. Taken together, BMSC-derived exosomal miR-9-3p suppressed the progression of bladder cancer through ESM1 downregulation, offering a potential novel therapeutic target for bladder cancer therapy.

A comparison of perioperative outcome between robot-assisted and laparoscopic radical prostatectomy: experience of a single institution

ABSTRACT Purpose To compare perioperative and pathological results in different approaches of robotic or laparoscopic radical prostatectomy. Materials and Methods We retrospectively reviewed 206 patients diagnosed with prostate cancer (PC) from June 2016 to October 2017 in the First Affiliated Hospital of Nanjing Medical University. A total of 132 cases underwent robot-assisted laparoscopic radical prostatectomy (RLRP) including 54 patients on transperitoneal robot-assisted laparoscopic radical prostatectomy (Tp-RLRP) and 78 on extraperitoneal robot-assisted laparoscopic radical prostatectomy (Ep-RLRP). Meanwhile, 74 patients performed with extraperitoneal laparoscopic radical prostatectomy (Ep-LPR) were also included. Perioperative and pathological data were compared among these groups. Results All operations were completed without conversion. There was no significant difference in basic and pathological characteristics of patients between each two groups. In Tp-RLRP vs. Ep-RLRP: Significant differences were found in the comparison in total operation time [235.98 ± 59.16 vs. 180.45 ± 50.27 min, P = 0.00], estimated blood loss (EBL) [399.07 ± 519.57 vs. 254.49 ± 308.05 mL, P = 0.0473], postoperative pelvic drainage time [5.37 ± 2.33 vs. 4.24 ± 3.08 d, P = 0.0237] and postoperative length of stay [8.15 ± 3.30 vs. 6.49 ± 3.49 d, P = 0.0068] while no significant differences were detected in other variables. In Ep-RLRP vs. Ep-LPR: Longer total operation time was observed in Ep-RLRP when compared to Ep-LPR [180.45 ± 50.27 vs. 143.80 ± 33.13 min, P = 0.000]. No significant differences were observed in other variables. Conclusion In RLRP, Ep-RLRP was proved a safe and effective approach based on the perioperative results compared to Tp-RLRP. Ep-RLRP and Ep-LPR provides equivalent perioperative and pathological outcomes.

A comparison of perioperative outcome between robot-assisted and laparoscopic radical prostatectomy: experience of a single institution.

PURPOSE: To compare perioperative and pathological results in different approaches of robotic or laparoscopic radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed 206 patients diagnosed with pros¬tate cancer (PC) from June 2016 to October 2017 in the First Affiliated Hospital of Nan¬jing Medical University. A total of 132 cases underwent robot-assisted laparoscopic radical prostatectomy (RLRP) including 54 patients on transperitoneal robot-assisted laparoscopic radical prostatectomy (Tp-RLRP) and 78 on extraperitoneal robot-assisted laparoscopic radical prostatectomy (Ep-RLRP). Meanwhile, 74 patients performed with extraperitoneal laparoscopic radical prostatectomy (Ep-LPR) were also included. Peri¬operative and pathological data were compared among these groups. RESULTS: All operations were completed without conversion. There was no signifi¬cant difference in basic and pathological characteristics of patients between each two groups. In Tp-RLRP vs. Ep-RLRP: Significant differences were found in the comparison in to¬tal operation time [235.98 ± 59.16 vs. 180.45 ± 50.27 min, P = 0.00], estimated blood loss (EBL) [399.07 ± 519.57 vs. 254.49 ± 308.05 mL, P = 0.0473], postoperative pelvic drainage time [5.37 ± 2.33 vs. 4.24 ± 3.08 d, P = 0.0237] and postoperative length of stay [8.15 ± 3.30 vs. 6.49 ± 3.49 d, P = 0.0068] while no significant differences were detected in other variables. In Ep-RLRP vs. Ep-LPR: Longer total operation time was observed in Ep-RLRP when compared to Ep-LPR [180.45 ± 50.27 vs. 143.80 ± 33.13 min, P = 0.000]. No significant differences were observed in other variables. CONCLUSION: In RLRP, Ep-RLRP was proved a safe and effective approach based on the perioperative results compared to Tp-RLRP. Ep-RLRP and Ep-LPR provides equivalent perioperative and pathological outcomes.

Long non-coding RNA NAP1L6 promotes tumor progression and predicts poor prognosis in prostate cancer by targeting Inhibin-ß A.

BACKGROUND/PURPOSE: Long non-coding RNAs (lncRNAs) have emerged as key molecules in initiation and progression of prostate cancer (PCa). In this study, we aimed to explore the role of lncRNA NAP1L6 in the development and progression of PCa. MATERIALS AND METHODS: We identified that lncRNA NAP1L6 was over-expressed both in PCa tissues and cell lines by gene expression array profiling. The expression level of NAP1L6 in 75 PCa tissues and adjacent tissues was detected by RT-PCR. Next, the correlations between NAP1L6 expression and clinical features of patients with PCa were analyzed by paired t-test or chi-squared test, and its association with patient prognosis was assessed by the Kaplan-Meier method. The effects of NAP1L6 on PC-3 and 22RV1 cells were evaluated by Cell Counting Kit-8 (CCK-8), migration, invasion, and colony formation assays. Further analysis of the results of the microarray was performed to find downstream gene of NAP1L6. Cell function experiments were performed in order to explore the relationship between NAP1L6 and Inhibin-ß A (INHBA) and the specific mechanism by which INHBA affects the development of PCa. RESULTS: Using microarray analysis, we identified 412 lncRNAs and 1245 mRNAs to be significantly differentially expressed in three PCa samples when compared with adjacent non-tumor tissues (ANTT) (fold-change ≥2.0 or ≤0.5, P<0.05, false discovery rate (FDR) <0.05). NAP1L6 expression was upregulated in PCa tissues and cell lines (both P<0.05) compared with ANTT. Besides, high expression level of NAP1L6 promotes PCa cell proliferation, migration, and invasion (all P<0.05), and is significantly associated with larger tumor diameter, distant metastasis, and shorter survival time (all P<0.05). We found that NAP1L6 promoted the expression of INHBA (P<0.05), and knockdown of NAP1L6 led to the reduction of PCa cell migration, invasion, and proliferation by regulating the expression of INHBA (all P<0.05). CONCLUSION: lncRNA NR6A1 might play an oncogenic role in PCa initiation and progression by regulating the expression of INHBA, and might act as a novel prognostic biomarker for PCa treatment.

TRIM36, a novel androgen-responsive gene, enhances anti-androgen efficacy against prostate cancer by inhibiting MAPK/ERK signaling pathways.

Hormone therapy drugs, such as bicalutamide and enzalutamide, directed against prostate cancer focus on androgen receptor (AR) signaling and are initially effective, but the disease progresses to lethality as resistance to these drugs develops. A method to prolong the drug response time and improve the drug efficacy is still unavailable. TRIM36 was reported as a novel androgen signaling target gene and is upregulated in prostate cancer. In this study, we found that 63.4% (64/95) of PCa in TMA expressed the TRIM36 protein. Interestingly, patients with negative TRIM36 expression had a shorter biochemical recurrence-free survival. TRIM36 expression was significantly associated with the Gleason score (P = 0.005), delayed prostate cancer cell cycle progression and inhibited cell proliferation in vitro and in vivo, and these effects were mediated via inhibition of the MAPK/ERK phosphorylation pathway. Remarkably, we found that rescuing the expression of TRIM36 during anti-androgen therapy could improve the drug efficacy. Collectively, TRIM36 is a novel androgen-responsive gene, and it dramatically enhanced the efficacy of anti-androgen drugs against prostate cancer.

The M6A methyltransferase METTL3: acting as a tumor suppressor in renal cell carcinoma.

We aimed to study the role of METTL3 in renal cell carcinoma (RCC) carcinogenesis and development. Immunohistochemistry was performed in clinical tissue microarray. Expression level of METTL3 in RCC tissues and cell lines was evaluated by quantitative real-time PCR (qRT-PCR) and western blot. Then, the effects of METTL3 on proliferation, migration, invasion and cell cycle were studied in RCC cells. Additionally, in vivo study was carried out in nude mice. Negative METTL3 expression was associated with larger tumor size (P=0.010) and higher histological grade (P=0.021). Moreover, RCC patients with positive METTL3 expression had an obvious longer survival time (P=0.039). METTL3 mRNA and protein expression was lower in RCC samples compared with adjacent non-tumor samples, and lower in RCC cell lines (CAKI-1, CAKI-2 and ACHN) compared with HK-2. Afterwards, knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest. In contrast, up-regulation of METTL3 could inhibit such functions and reduce G0/G1 arrest. Additionally, up-regulation of METTL3 significantly suppressed tumor growth in vivo. Furthermore, significant changes in epithelial-to-mesenchymal transition (EMT) and PI3K-Akt-mTOR pathways were observed. Overall, our findings demonstrated that METTL3 might have a carcinostasis role in cell proliferation, migration, invasion function and cell cycle of RCC, indicating METTL3 may act as a novel marker for tumorigenesis, development and survival of RCC.

BMI and serum lipid parameters predict increasing risk and aggressive prostate cancer in Chinese people.

OBJECTIVES: To determine if obesity and serum lipid parameters are associated with increased risk and more aggressive prostate cancer in Chinese population. MATERIALS AND METHODS: We conducted a retrospective cohort analysis including 3102 patients. Kruskal-Wallis test for continuous variables and the chi-squared tests for categorical variables were used for univariate comparison of the differences in patient characteristics across BMI categories between different groups. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for the association between prostate cancer and the various patient characteristics. Multivariable Cox proportional hazards regression was performed to assess the risk of prostate cancer recurrence. RESULTS: 974 consecutive men were diagnosed as prostate cancer and 700 patients subsequently received radical prostatectomy immediately, and 1031 patients were pathologically diagnosed as biopsy negative. The level of low-density-lipoprotein cholesterol (LDL-c) and total cholesterol was significantly higher and the high-density-lipoprotein cholesterol (HDL-c) level is much lower in prostate cancer patients. Patients with low level of HDL-c, who subsequently received radical prostatectomy, had increased risk of high risk disease. In addition, patients with normal weight were less likely to develop a biochemical recurrence. Combined analysis revealed that obese patients had significantly higher rates of PSA recurrence over time than nonobese patients. CONCLUSIONS: In our study, lipid parameters are supposed to be associated with prostate cancer risk and aggressiveness. Obese men are at increased risk of PSA recurrence after radical prostatectomy.