Long-term effect of acute ischemic injury on the kidney underwent clamped partial nephrectomy.

GFR reaches a new baseline, primarily correlating with nephron-mass preservation, 1-12 months after partial nephrectomy (PN). However, does the ipsilateral GFR experience subsequent decline, and does acute ischemic injury has long-term effect on the operated kidney? 319 patients with two kidneys and unilateral clamped PN were analyzed. All had preoperative, new-baseline, and latest follow-up imaging/serum creatinine levels. Annual ipsilateral GFR decline rate (AIGDR) was defined as new-baseline GFR minus latest follow-up GFR normalized by new-baseline GFR, per year. Spectrum score was used to reflect the degree of acute ischemic injury in the operated kidney. 100 subjects searching for health screening served as controls. Predictive factors for AIGDR were assessed. The median AIGDR was 2.25%, significantly higher than controls (0.88%, p = 0.036). With some contralateral hypertrophy, the global annual GFR decline was similar to that of controls (0.81% vs. 0.88%, p = 0.7). Spectrum score correlated significantly with AIGDR (p = 0.037). These results support that acute ischemic injury has long-term effect on the operated kidney.

Transcriptome-Wide Map of N6-Methyladenosine Methylome Profiling in Human Bladder Cancer.

N6-Methyladenosine (m6A) is the most widespread internal RNA modification in several species. In spite of latest advances in researching the biological roles of m6A, its function in the development and progression of bladder cancer remains unclear. In this study, we used MeRIPty -55-seq and RNA-seq methods to obtain a comprehensive transcriptome-wide m6A profiling and gene expression pattern in bladder cancer and paired normal adjacent tissues. Our findings showed that there were 2,331 hypomethylated and 3,819 hypermethylated mRNAs, 32 hypomethylated and 105 hypermethylated lncRNAs, and 15 hypomethylated and 238 hypermethylated circRNAs in bladder cancer tissues compared to adjacent normal tissues. Furthermore, m6A is most often harbored in the coding sequence (CDS), with some near the start and stop codons between two groups. Functional enrichment analysis revealed that differentially methylated mRNAs, lncRNAs, and circRNAs were mostly enriched in transcriptional misregulation in cancer and TNF signaling pathway. We also found that different m6A methylation levels of gene might regulate its expression. In summary, our results for the first time provide an m6A landscape of human bladder cancer, which expand the understanding of m6A modifications and uncover the regulation of mRNAs, lncRNAs, and circRNAs through m6A modification in bladder cancer.

Identifying Hypoxia Characteristics to Stratify Prognosis and Assess the Tumor Immune Microenvironment in Renal Cell Carcinoma.

Background: Renal cell carcinoma (RCC) is a common malignant tumor worldwide, and immune checkpoint inhibitors are a new therapeutic option for metastatic RCC. Infiltrating immune cells in the tumor microenvironment (TME) play a critical part in RCC biology, which is important for tumor therapy and prediction. Hypoxia is a common condition that occurs in the TME and may lead to RCC immunosuppression and immune escape. This study was conducted to analyze the extent of the hypoxia immune microenvironment in the TME of RCC and develop a hypoxia-related risk model for predicting the prognosis of patients with RCC. Methods: The gene expression profiles of 526 patients with RCC were downloaded from The Cancer Genome Atlas database. Combined with the hallmark-hypoxia gene dataset downloaded from Gene Set Enrichment Analysis, prognosis-related hypoxia genes were selected by survival analysis. A protein-protein interaction network and functional enrichment analysis were performed. A hypoxia-related risk model predicting the prognosis of patients with RCC was established using the least absolute shrinkage and selection operator. Data of 91 cases downloaded from the International Cancer Genome Consortium (ICGC) database were used for validation. CIBERSORT was applied to analyze the fractions of 22 immune cell types in the TME of RCC between low- and high-risk groups. The expression profiles of immunomodulators and immunosuppressive cytokines were also analyzed. Results: Ninety-three genes were significantly associated with poor overall survival of patients with RCC and were mainly involved in 10 pathways. Using the established hypoxia-related risk model, the receiver operating characteristic curves showed an accuracy of 76.1% (95% CI: 0.719-0.804), and Cox proportional hazards regression analysis revealed that the model was an independent predictor of the prognosis of patients with RCC [hazard ratio (HR) = 2.884; 95% CI: 2.090-3.979] (p < 0.001). Using the ICGC database, we verified that the low-risk score group had a better overall survival outcome than the high-risk group. Additionally, dividing the hypoxia risk score into high-risk and low-risk groups could predict the immune microenvironment of RCC. Conclusions: We demonstrated that a hypoxia-related risk model can be used to predict the outcomes of patients with RCC and reflect the immune microenvironment of RCC, which may help improve the overall clinical response to immune checkpoint inhibitors.

Silencing of the TRIM58 Gene by Aberrant Promoter Methylation is Associated with a Poor Patient Outcome and Promotes Cell Proliferation and Migration in Clear Cell Renal Cell Carcinoma.

To investigate the underlying molecular mechanism of tripartite motif-containing 58 (TRIM58) in the development of clear cell renal cell carcinoma (ccRCC), we explored TRIM58 expression and methylation in tumor tissues and the association with clinicopathological features and prognosis of tissue samples; Moreover, we examined the direct gene transcription of TRIM58-specific DNA demethyltransferase (TRIM58-TET1) by the CRISPR-dCas9 fused with the catalytic domain of TET1 and the biological functions in RCC cells. In this study, we demonstrate that TRIM58 is frequently downregulated by promoter methylation in ccRCC tissues, associated significantly with tumor nuclear grade and poor patient survival. TRIM58-TET1 directly induces demethylation of TRIM58 CpG islands, and activates TRIM58 transcription in RCC cell lines. Besides, DNA demethylation of TRIM58 by TRIM58-TET1 significantly inhibits cell proliferation and migration Overall, our results demonstrate that TRIM58 is inactivated by promoter methylation, associates with tumor nuclear grade and poor survival, and TRIM58 DNA demethylation could directly activate TRIM58 transcription and inhibit cell proliferation and migration in RCC cell lines.

Learning Curve of an Innovative "3-Port" Laparoscopic Radical Prostatectomy: A Single-Center Analysis from 2016 to 2019.

BACKGROUND: "Three-port" laparoscopic radical prostatectomy (LRP) has been applied as a substitution for the conventional 4- to 5-port LRP to treat prostate cancer (PCa) patients in our institution. OBJECTIVE: To evaluate the learning curve of an innovative "3-port" LRP for PCa patients. METHODS: 206 patients who received "3-port" LRP were retrospectively reviewed between January 2016 and December 2019 at our institution. According to the different years of operations performed, all of the patients were divided into group A (No. 1-50), group B (No. 51-107), group C (No. 108-160), and group D (No. 161-206). A learning curve was depicted by analyzing the parameters of operative time (OT), estimated blood loss (EBL), hospitalization, and drainage indwelling days. RESULTS: All groups were comparable with regard to the preoperative characteristics (p > 0.05). The sloping learning curve for the surgeon showed that OT and EBL were strongly correlated with an accumulated experience when compared between group A and the other groups (p < 0.05), denoting that the surgical skill of the "3-port" LRP can be fully mastered after around 50 cases. Although no significant correlation with additional experience was observed in the hospitalization and drainage indwelling days among groups, a tendency towards less hospitalization and drainage indwelling days was still reflected. CONCLUSIONS: Our 4-year analysis based on a single-center experience exhibits that the innovative "3-port" LRP appears to be favorable with decreasing tendency in OT and EBL with experience accumulation. In view of its advantage of perioperative parameters with an evidently improved learning curve, it should be recommended in the clinical practice!

Renal Ewing's sarcoma/primitive neuroectodermal tumor (PNET): a case series of 7 patients and literature review.

BACKGROUND: Primitive neuroectodermal tumor (PNET) is a rare kind of sarcoma that is primarily found in the kidney and has a very poor prognosis. Here, we review and summarize the clinical data of patients with renal PNET in our center and follow up the patients for survival status. Although the current literature suggests that chemotherapy may benefit the survival of these patients, the information from our center suggests that this may not be the case. METHODS: We retrospectively analyzed the clinical data of patients with renal PNET diagnosed pathologically at Peking University First Hospital from January 1, 2007, to January 1, 2018. All of the patients were followed up for survival status. RESULTS: Seven patients with renal PNET were found. The ratio of males to females was 6:1. The median age was 29 years (21-72 years) at the time of diagnosis. The preoperative imaging examination showed a large renal mass protruding outwards from the renal contour, with internal necrosis and hemorrhage. Six/7 patients were diagnosed with distant metastasis or retroperitoneal lymph node metastasis. The main clinical manifestations of patients were pain (5/7) and fever (3/7). In immunohistochemistry, all patients' samples were CD99 positive. All patients died in our follow-up, with an average overall survival (OS) of 12.09 months (1.90-26.77 months). CONCLUSIONS: As a rare renal tumor, renal PNET has a propensity to occur in young males. Most patients have distant metastasis when they are diagnosed, and the prognosis is very poor. Effective treatments are urgently needed.

Aberrant methylation of the 16q23.1 tumor suppressor gene ADAMTS18 promotes tumorigenesis and progression of clear cell renal cell carcinoma.

BACKGROUND: The 16q23.1 tumor suppressor gene (TSG) of ADAMTS18 has been identified to be aberrant methylated in clear cell renal cell carcinoma (ccRCC), and there still exists an unclear situation between its methylation and the progression of ccRCC. OBJECTIVE: To analyze the biological function and mechanism of ADAMTS18 gene in the tumorigenesis and progression of ccRCC. METHODS: We examined ADAMTS18 gene methylation using methylation- specific polymerase chain reaction (MSP) in 92 ccRCC primary tumors from September 2017 to May 2018. Using reverse transcriptase PCR (RT-PCR) and immunohistochemical (IHC) assay, the relative expression level of ADAMTS18 was measured in the representative tumor samples with their adjacent normal tissues. Meanwhile, colony formation, cell viability, wound healing, transwell chamber, flow cytometry, and PI staining were performed to confirm the tumor-suppressive function and mechanism of ADAMTS18 gene. RESULTS: Aberrant methylation was further detected in 47 of the 92 (51.1%) primary tumors and in 8 of the 92 (8.7%) adjacent normal tissues (p < 0.05). Due to the phenomenon of aberrant methylation, ectopic low-level expression of ADAMTS18 gene could result in the promotion of tumorigenesis and progression in ccRCC. CONCLUSION: The aberrantly methylated ADAMTS18 gene may be involved in the tumorigenesis and progression of ccRCC.

Synthetic Artificial Long Non-coding RNA Shows Higher Efficiency in Specific Malignant Phenotype Inhibition Compared to the CRISPR/Cas Systems.

Objective: Both oncogenic transcription factors (TFs) and microRNAs (miRNAs) play an important regulator in human cancer by transcriptional and post-transcriptional regulation, respectively. These phenomena raise questions about the ability of artificial device to regulate miRNAs and TFs simultaneously. In this study, we aimed to construct an artificial long non-coding RNA, "alncRNA," which imitated CRISPR/Cas systems and to illuminate its therapeutic effects in bladder cancer cell lines. At the same time, we also compared the efficiency of alncRNA and CRISPR/Cas systems in regulating gene expression. Study Design and Methods: Based on engineering principles of synthetic biology, we combined tandem arrayed cDNA sequences of aptamer for TFs with tandem arrayed cDNA copies of binding sites for the miRNAs to construct alncRNA. In order to prove the utility of this platform, we chose ß -catenin, NF-κB, miR-940, and miR-495 as the functional targets and used the bladder cancer cell lines 5637 and T24 as the test models. Real-time Quantitative PCR (qPCR), dual-luciferase assay and relative phenotypic experiments were applied to severally test the expression of relative gene and therapeutic effects of our devices. Result: Dual-luciferase assay indicated alncRNA could inhibit transcriptional activity of TFs. What's more, the result of qPCR showed that expression levels of the relative TFs target genes and miRNAs were reduced by corresponding alncRNA and the inhibitory effect was better than CRIPSR dCas9-KRAB. By functional experiments, decreased cell proliferation, increased apoptosis, and motility inhibition were observed in alncRNA-infected bladder cells. Conclusion: In summary, our synthetic devices indeed function as anti-tumor regulator, which synchronously accomplish transcriptional and post-transcriptional regulation in bladder cancer cell and show higher efficiency in specific malignant phenotype inhibition compared to the CRISPR/Cas systems. Most importantly, Anti-cancer effects were induced by the synthetic alncRNA in the bladder cancer lines. Our devices, therefore, provides a novel strategy for cancer therapy and could be a useful "weapon" for cancer cell.

Acute kidney injury in solitary kidney patients after partial nephrectomy: incidence, risk factors and prediction.

BACKGROUND: To analyze the incidence and risk factors of acute kidney injury (AKI) after partial nephrectomy (PN) in patients with solitary kidney, and to build AKI prediction models using logistic regression and machine learning (ML) approaches. METHODS: Clinical data of 87 solitary kidney patients with renal mass who received PN from January 2003 to March 2019 were collected. The diagnosis of AKI was based on KDIGO criteria. Logistic regression analysis and ML method were used to build prediction models. RESULTS: AKI developed in 52 (59.8%) patients. The logistic regression model had three variables: ischemia time (P=0.003), surgery time (P=0.001) and preoperative fasted blood glucose level (FBG) (P=0.049). The area under curve (AUC) was 0.826, with the specificity and sensitivity of optimal threshold value 82.9% and 69.2%. The ML model had the following variables: ischemia time, surgery time, age, FBG, mean arterial pressure (MAP), colloid, crystalloid, etc. XGBoost model has the best prediction performance. The AUC was 0.749, lower than that of the logistic regression model with no statistical difference (P=0.258), with the specificity and sensitivity 62.9% and 84.6%, respectively. CONCLUSIONS: The incidence of AKI after PN in patients with a solitary kidney was relatively high, it was associated with longer ischemia time, surgery time and higher FBG level, etc. The performance of ML model had no significant difference with logistic regression model. Prospective studies with larger sample sizes are awaited to test and verify our research findings.

The prognostic value of preoperative controlling nutritional status score in non-metastatic renal cell carcinoma treated with surgery: a retrospective single-institution study.

PURPOSE: This study aimed to investigate the significance of the controlling nutritional status (CONUT) score as a predictor for survival outcomes for non-metastatic renal cell carcinoma (RCC) patients. METHODS: We retrospectively reviewed 325 patients who received surgical treatment for renal cell carcinoma between 2010 and 2012 at Peking University First Hospital. Patients were divided into two groups according to the optimal cut-off value of CONUT score. Kaplan-Meier method and log-rank test were used for survival analysis according to different CONUT groups. Cox proportional hazards regression models were performed to assess the prognostic value of clinicopathological parameters for overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) respectively. RESULTS: The optimal cut-off value of CONUT score was 3. High CONUT score significantly correlated to higher tumor grade (P<0.001), later pathological T stage (P<0.001) and tumor necrosis (P<0.001). Patients with higher CONUT score had worse OS (HR 5.34, 95% CI 2.29-12.46, P<0.001), CSS (HR 5.51, 95% CI 2.12-14.33, P<0.001) and DFS (HR 4.23, 95% CI 2.16-8.29, P<0.001). In multivariable analysis, high CONUT score was an independent risk factor for OS, CSS and DFS (OS: HR=3.36, 95% CI 1.73-6.56, P<0.001; CSS: HR=3.34, 95% CI 1.59-6.98, P=0.001; DFS: HR=1.85, ]95% CI 1.07-3.21, P=0.029). CONCLUSION: Preoperative CONUT score was an independent prognostic factor for OS, CSS and DFS in non-metastatic RCC patients treated with surgery.

Short-term benefit of neoadjuvant hormone therapy in patients with localized high-risk or limited progressive prostate cancer.

Purpose: Radical surgery is the preferred method for local high-risk and limited progressive prostate cancer in the routine clinical setting. However, current guidelines do not recommend neoadjuvant hormone therapy (NHT). Opinions regarding NHT vary among individual clinicians. According to the experience gained at our center, we explored the benefits of NHT for patients with prostate cancer during the perioperative period in this study. Methods: In this retrospective study, we explored the perioperative benefits of NHT among 189 patients with local high-risk or limited progressive prostate cancer who underwent radical prostatectomy and divided them into two groups: the NHT group and the non-NHT group. The NHT regimens were a gonadotropin-releasing hormone (GnRH) agonist alone (3.75/11.25 mg of leuprolide or 3.6/10.8 mg of goserelin acetate), an androgen receptor antagonist (ARA) alone, or a combination of the two. The duration of treatment was <3 months, 3 to 6 months, or >6 months. Results: We found that NHT could reduce the surgery time and intraoperative hemorrhage, thus reducing the difficulty of surgery; NHT could also improve the postoperative recovery of patients. However, it did not reduce the stage of prostate cancer or positive surgical margin rate. Conclusions: Neoadjuvant therapy is optional for some patients. We believe that NHT will improve the overall prognosis of patients as progress continues in the medical field in the future.

The Prognostic Value of Pretreatment Plasma Fibrinogen in Urological Cancers: A Systematic Review and Meta-analysis.

Objective: Growing evidence suggests pretreatment fibrinogen can serve as a prognostic marker in various malignancies. However, there are contradictory results about the prognostic role of fibrinogen in urological cancers. We conducted a meta-analysis to evaluate the association between pretreatment plasma fibrinogen and survival outcomes in urological cancers. Methods: After a systematic search of PubMed and Embase, we included 14 studies in our meta-analysis, and estimated hazard ratios (HRs) for overall survival (OS) and cancer-specific survival (CSS) using a fixed-effect model. Results: Our results indicate that pretreatment plasma fibrinogen is a prognostic factor in urological cancers (OS: HR=2.21, 95% CI=1.91-2.57, P<0.001, CSS: HR=2.67, 95% CI=2.23-3.19, P<0.001). Elevated pretreatment plasma fibrinogen is associated with poorer survival in prostate cancer (OS: HR=2.26, 95% CI=1.47-3.48, P<0.001; CSS: HR=2.42, 95% CI=1.44-4.07, P=0.001), renal cell carcinoma (OS: HR=2.13, 95% CI=1.75-2.61, P<0.001; CSS: HR=2.99, 95% CI=2.29-3.89, P<0.001) and upper tract urothelial carcinoma (OS: HR=2.34, 95% CI=1.81-3.02, P<0.001; CSS: HR=2.43, 95% CI=1.84-3.20, P<0.001). Subgroup analyses showed that plasma fibrinogen has a more negative impact on survival in Caucasian patients (OS: HR=2.52, 95% CI=1.95-3.25, P<0.001; CSS: HR=2.83, 95% CI=1.92-4.17, P<0.001) than Asian patients (OS: HR=2.07, 95% CI=1.73-2.49, P<0.001; CSS: HR=2.63, 95% CI=2.14-3.22, P<0.001). The prognostic value of fibrinogen is also consistent when stratified by different cut-off values. Conclusions: These results show that high pretreatment plasma fibrinogen levels can predict poorer OS and CSS in patients with urological cancers.

Preoperative PROSTATE scoring system: a potential predictive tool for the risk of biochemical recurrence after radical prostatectomy.

PURPOSE: To study the association between the preoperative PROSTATE scoring system and the prediction of biochemical recurrence (BCR) risk, after radical prostatectomy (RP) in prostate cancer patients. PATIENTS AND METHODS: A total of 340 patients who underwent a laparoscopic radical prostatectomy in Peking University First Hospital between November 2007 and March 2016 were included in the study. The preoperative PROSTATE scoring system was measured and calculated. The performance of the scoring system to predict BCR risk was estimated using the receiver operating characteristic curve (ROC curve). BCR-free survival was analyzed using the Kaplan- Meier method, and the log-rank test was applied to compare the differences in risk among the patient groups. The Cox proportional hazards regression was used to analyze the performance of the grouped PROSTATE scores. RESULTS: Of the total population, 91 (26.8%) patients had BCR. The PROSTATE score was significantly different between the BCR-developed and BCR-free groups (P<0.001). The ROC curve analysis of the scoring system showed an accuracy of 70.7% (95% CI 0.643-0.771) (P<0.001). The percentage of BCR in the high-risk (10-15), moderate-risk (5-9) and low-risk (0-4) groups was 63.3%, 24.6% and 10.3% respectively (P<0.001). The Cox proportional hazards regression analysis revealed that the grouped score was an independent predictor of BCR after RP (HR=2.002; 95% CI 1.222-3.280) (P=0.006). CONCLUSION: The PROSTATE scoring system performed adequately in predicting the risk of BCR after RP. The scoring system can assist in decision-making about the operation and post- operative follow-up for patients with high-risk.

The Institute of Urology, Peking University prostatectomy score: a simple preoperative classification of prostate cancer for predicting surgical difficulty and risk.

Traditional laparoscopic radical prostatectomy is a treatment choice in many developing countries and regions for most patients with localized prostate cancer; however, no system for predicting surgical difficulty and risk has been established. This study aimed to propose a simple and standard preoperative classification system of prostate cancer using preoperative data to predict surgical difficulty and risk and to evaluate the relationship between the data and postoperative complications. We collected data from 236 patients and divided them into three groups to evaluate and validate the relationships among preoperative, operative, and postoperative data. This new scoring system is based on the body mass index, ultrasonic prostate volume, preoperative prostate-specific antigen level, middle lobe protrusion, and clinical stage. In the scoring group, we classified 89 patients into two groups: the low-risk group (score of <4) and high-risk group (score of ≥4), and then compared the postoperative data between the two groups. The positive surgical margin rate was higher in the high-risk group than low-risk group. The results in validation Groups A and B were similar to those in the scoring group. The focus of our scoring system is to allow for preliminary assessment of surgical difficulty by collecting the patients' basic information. Urologists can easily use the scoring system to evaluate the surgical difficulty and predict the risks of a positive surgical margin and urinary incontinence in patients undergoing laparoscopic radical prostatectomy.