Prognostic value of Controlling Nutritional Status score for postoperative complications and biochemical recurrence in prostate cancer patients undergoing laparoscopic radical prostatectomy.

Background: Controlling Nutritional Status (CONUT) score was used for screening the preoperative nutritional status. The correlation between the CONUT score and the prognosis of patients with prostate cancer (PCa) has yet to be elucidated. Herein, we analyzed the prognostic value of CONUT scores in patients with PCa who underwent laparoscopic radical prostatectomy. Materials and methods: Data of 244 patients were retrospectively evaluated. Perioperative variables and follow-up data were analyzed. The patients were categorized into 2 groups according to their preoperative CONUT scores. Postoperative complication and incontinence rates were also compared. The Kaplan-Meier method was used to estimate the median biochemical recurrence-free survival (BCRFS) between the 2 groups. Univariate and multivariate Cox regression analyses were performed to identify the potential prognostic factors for BCRFS. Results: Patients were categorized into the low-CONUT group (CONUT score <3, n = 207) and high-CONUT group (CONUT score ≥3, n = 37). The high-CONUT group had a higher overall complication rate (40.5% vs.19.3%, p = 0.004), a higher major complication rate (10.8% vs. 3.9%, p = 0.013), and longer postoperative length of stay (8 days vs. 7 days, p = 0.017). More fever, urinary infection, abdominal infection, scrotal edema, rash, and hemorrhagic events (all p values < 0.05) were observed in the high-CONUT group. A higher rate of urinary incontinence was observed in the high-CONUT group at 1 (34.4% vs. 13.2%, p = 0.030) and 3 months (24.1% vs. 8.2%, p = 0.023) postoperatively. The high-CONUT group had shorter medium BCRFS (23.8 months vs. 54.6 months, p = 0.029), and a CONUT score ≥3 was an independent risk factor for a shorter BCRFS (hazards ratio, 1.842; p = 0.026). Conclusions: The CONUT score is a useful predictive tool for higher postoperative complication rates and shorter BCRFS in patients with PCa who undergo laparoscopic radical prostatectomy.

Cancer-associated fibroblast exosomes promote prostate cancer metastasis through miR-500a-3p/FBXW7/HSF1 axis under hypoxic microenvironment.

Metastasis is the main cause of deaths in prostate cancer (PCa). However, the exact mechanisms underlying PCa metastasis are not fully understood. In this study, we discovered pronounced hypoxia in primary lesions of metastatic PCa(mPCa). The exosomes secreted by cancer-associated fibroblasts (CAFs) under hypoxic conditions significantly enhance PCa metastasis both in vitro and in vivo. Through miRNA sequencing and reverse transcription quantitative PCR (RT-qPCR), we found that hypoxia elevated miR-500a-3p levels in CAFs exosomes. Subsequent RT-qPCR, western blotting, and dual luciferase reporter assays identified F-box and WD repeat domain-containing 7(FBXW7) as a target of miR-500a-3p. In addition, immunohistochemistry revealed that FBXW7 expression decreased with the progression of PCa, while heat shock transcription factor 1(HSF1) expression increased. Introducing an FBXW7 plasmid into PCa cells reduced their metastatic potential and significantly lowered HSF1 expression. These findings suggest that CAFs exosomes drive PCa metastasis via the miR-500a-3p/FBXW7/HSF1 axis in a hypoxic microenvironment. Targeting either hypoxia or exosomal miR-500a-3p could be a promising strategy for PCa management.

Immune landscape in rejection of renal transplantation revealed by high-throughput single-cell RNA sequencing.

Background: The role of the cellular level in kidney transplant rejection is unclear, and single-cell RNA sequencing (scRNA-seq) can reveal the single-cell landscape behind rejection of human kidney allografts at the single-cell level. Methods: High-quality transcriptomes were generated from scRNA-seq data from five human kidney transplantation biopsy cores. Cluster analysis was performed on the scRNA-seq data by known cell marker genes in order to identify different cell types. In addition, pathways, pseudotime developmental trajectories and transcriptional regulatory networks involved in different cell subpopulations were explored. Next, we systematically analyzed the scoring of gene sets regarding single-cell expression profiles based on biological processes associated with oxidative stress. Results: We obtained 81,139 single cells by scRNA-seq from kidney transplant tissue biopsies of three antibody-mediated rejection (ABMR) patients and two acute kidney injury (AKI) patients with non-rejection causes and identified 11 cell types, including immune cells, renal cells and several stromal cells. Immune cells such as macrophages showed inflammatory activation and antigen presentation and complement signaling, especially in rejection where some subpopulations of cells specifically expressed in rejection showed specific pro-inflammatory responses. In addition, patients with rejection are characterized by an increased number of fibroblasts, and further analysis of subpopulations of fibroblasts revealed their involvement in inflammatory and fibrosis-related pathways leading to increased renal rejection and fibrosis. Notably, the gene set score for response to oxidative stress was higher in patients with rejection. Conclusion: Insight into histological differences in kidney transplant patients with or without rejection was gained by assessing differences in cellular levels at single-cell resolution. In conclusion, we applied scRNA-seq to rejection after renal transplantation to deconstruct its heterogeneity and identify new targets for personalized therapeutic approaches.

MRI-measured periprostatic adipose tissue volume as a prognostic predictor in prostate cancer patients undergoing laparoscopic radical prostatectomy.

In this study, we evaluated the association between the PPAT volume and the prognosis of PCa patients after LRP. We retrospectively analysed data of 189 PCa patients who underwent LRP in Beijing Chaoyang Hospital. Volumes of PPAT and prostate were measured by magnetic resonance imaging (MRI), and normalized PPAT volume was computed (PPAT volume divided by prostate volume). Patients were then stratified into the high-PPAT group (n = 95) and low-PPAT group (n = 94) by the median of normalized PPAT volume (73%). The high-PPAT group had significantly higher Gleason score (total score 8 or more, 39.0% vs. 4.3%, p < 0.001) and pathological stage (stage T3b, 28.4% vs. 13.8%, p = 0.048). No significant correlation between normalized PPAT volume and body mass index (ρ = -0.012, p = 0.872) was observed. Kaplan-Meier curve analysis showed the high-PPAT group had significantly shorter biochemical recurrence (BCR) interval (median progression-free survival time 15.9 months vs. 32.7 months, p = 0.001). Univiarate and multivariate Cox regression analyses showed high normalized PPAT volume (>73%) (hazard ratio 1.787 [1.075-3.156], p = 0.002) were independent risk factors for BCR post-operatively. In conclusion, MRI-measured PPAT volume is of significant prognostic value for PCa patients undergoing LRP.

Skull metastasis is a poor prognostic factor for prostate cancer patients with bone metastasis: a retrospective study based on a Chinese population.

BACKGROUND: Skull is a relatively rare metastasis site for prostate cancer (PCa). There is no evidence regarding the prognostic indication of skull metastasis (SM) in PCa patients. In this study, we analyzed the prognostic value of SM for metastatic PCa patients receiving androgen deprivation therapy (ADT). METHODS: 107 consecutive patients were included from September 2008 to August 2021. All patients were administered with standard ADT. Abiraterone plus glucocorticoid and/or docetaxel chemotherapy were given after failure to castration-resistant prostate cancer. Clinical parameters and follow-up prognostic data were retrospectively analyzed. The association of clinical and pathological parameters with SM were analyzed. The progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier analysis and Cox regression analyses. RESULTS: Patients with SM (n = 26) had significantly higher biopsy Gleason scores, higher clinical T stage, higher prostate-specific antigen level at diagnosis, and were more likely to have high-burden metastasis and lymph node metastasis, compared with those without SM (n = 81). They also showed significantly lower level of hemoglobin, albumin and serum calcium, along with higher level of alkaline phosphatase. SM was significantly associated with shorter medium PFS (9.4 vs. 18.3 months, p < 0.001) and OS (22.2 vs. 58.2 months, p < 0.001). Cox analysis demonstrated that SM was an independent risk factor for shorter PFS (hazard ratio 2.327 [1.429-3.789], p = 0.001) and shorter OS (hazard ratio 2.810 [1.615-4.899], p < 0.001). CONCLUSION: In this study, we found that SM was significantly correlated with more aggressive disease and indicated poor prognosis in PCa patients with bone metastasis. Our study may provide useful reference for the risk stratification of PCa patients.

MRI-measured adipose features as predictive factors for detection of prostate cancer in males undergoing systematic prostate biopsy: a retrospective study based on a Chinese population.

In this study, we retrospectively evaluated the data of 901 men undergoing ultrasonography-guided systematic prostate biopsy between March 2013 and May 2022. Adipose features, including periprostatic adipose tissue (PPAT) thickness and subcutaneous fat thickness, were measured using MRI before biopsy. Prediction models of all PCa and clinically significant PCa (csPCa) (Gleason score higher than 6) were established based on variables selected by multivariate logistic regression and prediction nomograms were constructed. Patients with PCa had higher PPAT thickness (4.64 [3.65-5.86] vs. 3.54 [2.49-4.51] mm, p < 0.001) and subcutaneous fat thickness (29.19 [23.05-35.95] vs. 27.90 [21.43-33.93] mm, p = 0.013) than those without PCa. Patients with csPCa had higher PPAT thickness (4.78 [3.80-5.88] vs. 4.52 [3.80-5.63] mm, p = 0.041) than those with non-csPCa. Adding adipose features to the prediction models significantly increased the area under the receiver operating characteristics curve for the prediction of all PCa (0.850 vs. 0.819, p < 0.001) and csPCa (0.827 vs. 0.798, p < 0.001). Based on MRI-measured adipose features and clinical parameters, we established two nomograms that were simple to use and could improve patient selection for prostate biopsy in Chinese population.