Development and validation of a clinical-radiomics model for prediction of prostate cancer: a multicenter study.

PURPOSE: To develop an early diagnosis model of prostate cancer based on clinical-radiomics to improve the accuracy of imaging diagnosis of prostate cancer. METHODS: The multicenter study enrolled a total of 449 patients with prostate cancer from December 2017 to January 2022. We retrospectively collected information from 342 patients who underwent prostate biopsy at Minhang Hospital. We extracted T2WI images through 3D-Slice, and used mask tools to mark the prostate area manually. The radiomics features were extracted by Python using the "Pyradiomics" module. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for data dimensionality reduction and feature selection, and the radiomics score was calculated according to the correlation coefficients. Multivariate logistic regression analysis was used to develop predictive models. We incorporated the radiomics score, PI-RADS, and clinical features, and this was presented as a nomogram. The model was validated using a cohort of 107 patients from the Xuhui Hospital. RESULTS: In total, 110 effective radiomics features were extracted. Finally, 9 features were significantly associated with the diagnosis of prostate cancer, from which we calculated the radiomics score. The predictors contained in the individualized prediction nomogram included age, fPSA/tPSA, PI-RADS, and radiomics score. The clinical-radiomics model showed good discrimination in the validation cohort (C-index = 0.88). CONCLUSION: This study presents a clinical-radiomics model that incorporates age, fPSA/PSA, PI-RADS, and radiomics score, which can be conveniently used to facilitate individualized prediction of prostate cancer before prostate biopsy.

A novel mini-retractor for retroperitoneal laparoscopic partial nephrectomy.

BACKGROUND: Retroperitoneal partial nephrectomy (RLPN) is the premier treatment for localized renal tumors despite narrow operation space. Many efforts have been taken to facilitate the operation of RLPN, but the optimal resolution remains debatable. OBJECTIVE: To explore the feasibility of using Mini-lap to improve workspace and surgical vision in RLPN. DESIGN, SETTING, AND PARTICIPANTS: A multicenter retrospective review of 51 patients who underwent RLPN with Mini-lap from January 2018 to December 2020 was conducted. SURGICAL PROCEDURE: Standard RLPN under three poles was performed in all cases. We highlighted the usage of Mini-lap (Teleflex Minilap percutaneous Surgical System) as a novel retractor in RLPN. OUTCOME AND MEASUREMENTS AND STATICAL ANALYSIS: Demographics, preoperative, intraoperative, and postoperative outcomes were assessed. RESULTS AND LIMITATIONS: All 51 cases completed RLPN with three ports successfully and no conversion to open surgery. The mean diameter of tumors was (3.53 ± 1.05) cm, in which 62.7% (32/51) were located anteriorly. The operation time and warm ischemic time (WIT) were (86.7 ± 15.9) min and (25.6 ± 5) min respectively. Minor complications (Clavien grade 1-2) occurred in 6 cases. The limitations were small sample size, retrospective design, and absence of control. CONCLUSIONS: Mini-lap could be used as a mini-retractor in RLPN, sparing extra assistant ports, expanding workspace, and optimizing vision. PATIENT SUMMARY: With highlights of larger workspace and less instrument interference, mini-lap could be applied in retroperitoneal laparoscopic partial nephrectomy.

Metabolic heterogeneity in clear cell renal cell carcinoma revealed by single-cell RNA sequencing and spatial transcriptomics.

BACKGROUND: Clear cell renal cell carcinoma is a prototypical tumor characterized by metabolic reprogramming, which extends beyond tumor cells to encompass diverse cell types within the tumor microenvironment. Nonetheless, current research on metabolic reprogramming in renal cell carcinoma mostly focuses on either tumor cells alone or conducts analyses of all cells within the tumor microenvironment as a mixture, thereby failing to precisely identify metabolic changes in different cell types within the tumor microenvironment. METHODS: Gathering 9 major single-cell RNA sequencing databases of clear cell renal cell carcinoma, encompassing 195 samples. Spatial transcriptomics data were selected to conduct metabolic activity analysis with spatial localization. Developing scMet program to convert RNA-seq data into scRNA-seq data for downstream analysis. RESULTS: Diverse cellular entities within the tumor microenvironment exhibit distinct infiltration preferences across varying histological grades and tissue origins. Higher-grade tumors manifest pronounced immunosuppressive traits. The identification of tumor cells in the RNA splicing state reveals an association between the enrichment of this particular cellular population and an unfavorable prognostic outcome. The energy metabolism of CD8+ T cells is pivotal not only for their cytotoxic effector functions but also as a marker of impending cellular exhaustion. Sphingolipid metabolism evinces a correlation with diverse macrophage-specific traits, particularly M2 polarization. The tumor epicenter is characterized by heightened metabolic activity, prominently marked by elevated tricarboxylic acid cycle and glycolysis while the pericapsular milieu showcases a conspicuous enrichment of attributes associated with vasculogenesis, inflammatory responses, and epithelial-mesenchymal transition. The scMet facilitates the transformation of RNA sequencing datasets sourced from TCGA into scRNA sequencing data, maintaining a substantial degree of correlation. CONCLUSIONS: The tumor microenvironment of clear cell renal cell carcinoma demonstrates significant metabolic heterogeneity across various cell types and spatial dimensions. scMet exhibits a notable capability to transform RNA sequencing data into scRNA sequencing data with a high degree of correlation.

Nitrogen addition strengthens the stabilizing effect of biodiversity on productivity by increasing plant trait diversity and species asynchrony in the artificial grassland communities.

Background and aims: Nitrogen (N) enrichment usually weakens the stabilizing effect of biodiversity on productivity. However, previous studies focused on plant species richness and thus largely ignored the potential contributions of plant functional traits to stability, even though evidence is increasing that functional traits are stronger predictors than species richness of ecosystem functions. Methods: We conducted a common garden experiment manipulating plant species richness and N addition levels to quantify effects of N addition on relations between species richness and functional trait identity and diversity underpinning the 'fast-slow' economics spectrum and community stability. Results: Nitrogen addition had a minor effect on community stability but increased the positive effects of species richness on community stability. Increasing community stability was found in the species-rich communities dominated by fast species due to substantially increasing temporal mean productivity relative to its standard deviation. Furthermore, enhancement in 'fast-slow' functional diversity in species-rich communities dominated by fast species under N addition increased species asynchrony, resulting in a robust biodiversity-stability relationship under N addition the artificial grassland communities. Conclusion: The findings demonstrate mechanistic links between plant species richness, 'fast-slow' functional traits, and community stability under N addition, suggesting that dynamics of biodiversity-stability relations under global changes are the results of species-specific responses of 'fast-slow' traits on the plant economics spectrum.

The Expression of miR-205 in Prostate Carcinoma and the Relationship with Prognosis in Patients.

Purpose: We aimed to investigate the changes of serum and cell exosome miR-205 levels in patients with prostate carcinoma and its clinical significance. Materials and Methods: Firstly, pronouncement of miR-205 in normal and prostate carcinoma tissues was analyzed by using UALCAN database. The relationship between miR-205 in tumor tissues and the pathological and clinical characteristics of patients with prostate carcinoma were analyzed. Consequently, 60 people with prostate carcinoma were collected to the Minhang Hospital from August 2016 to August 2021. Serum of patients in the two groups was collected, and RNA in serum exosomes was extracted, and qRT-PCR was used to analyze the expression of miR-205 mediated by serum exosomes. Meanwhile, the relationship among the clinical as well as pathological aspects and bodement of patients with prostate carcinoma and the pronouncement level of miR-205 mediated by exosome was compared. Next, assays like wound healing and CKK-8 were used to investigate the effects of miR-205 in exosomes extracted from prostate carcinoma on the augmentation and metastasis of prostate carcinoma. Results: The results showed that the pronouncement level of miR-205 in tissues with prostate carcinoma was significantly lower than that in normal prostate tissues. In addition, the pronouncement level of miR-205 in fluid exosome of people with prostate carcinoma and exosomes derived from the lines of prostate carcinoma was considerably less than that in serum exosomes of healthy patients and that of normal cell lines of prostate. The pronouncement level of miR-205 in fluid exosomes of people with prostate carcinoma was negatively associated with cancer phase, uncontrolled cell division in lymph nodes, distant metastasis, and PSA level at initial diagnosis. Analysis (multivariate and univariate) showed that miR-205 pronouncement was a sovereign threat cause for prognosis of prostate cancer patients. Additionally, the pronouncement and metastasis of prostate carcinoma can be restricted by the overexpression of miR-205. Conclusion: The pronouncement of miR-205 in liquid derived exosomes is correlated with the prediction of people with prostate carcinoma and may be a new marker for identification and cure of prostate carcinoma.

Docetaxel chemotherapy plus androgen-deprivation therapy in high-volume disease metastatic hormone-sensitive prostate cancer in Chinese patients: an efficacy and safety analysis.

OBJECTIVE: To investigate the efficacy and safety of docetaxel chemotherapy combined with androgen-deprivation therapy for patients with high-volume disease metastatic hormone-sensitive prostate cancer. METHODS: 153 cases of high-volume disease metastatic hormone-sensitive prostate cancer in Minhang Hospital between January 2018 and December 2019 were analyzed retrospectively, including the number of patients, age, initial PSA level, Gleason score, TNM stage and ECOG score. 90 patients in the endocrine therapy group received continuous ADT, and 63 patients in the combined chemotherapy group received docetaxel plus ADT. The progression-free survival time (time from initiation of prostate cancer treatment to progression to CRPC), PSA response rate, and adverse reactions were compared between the two groups. RESULTS: All 153 cases were closely followed up for a period of 12.3-35.3 months, with a median follow-up time of 23.5 months. The median time to reach the lowest point of PSA in the two groups was 6.3 months and 7.9 months (P = 0.018) in the combination chemotherapy group and the ADT group alone, with 27 (42.9%) and 12 (13.3%) cases in the two groups Within 12 months of treatment, PSA decreased to below 0.2 ng/ml (P = 0.02), and progression-free survival was 16.9 months (6.5-28.5 months) and 11.2 months (4.3-22.7 months) in the two groups. (P < 0.001). There were 18 cases (28.6%) and 54 cases (60%) in the two groups with disease progression (P < 0.001). There were 6 cases (9.5%) and 15 cases (16.7%) in the combination chemotherapy group and the ADT group died of prostate cancer and related complications, respectively. All 63 cases in the combined chemotherapy group completed 6 cycles of chemotherapy. 39 (61.9%) cases experienced varying degrees of neutropenia, of which 12 (19%) experienced grade 3-4 neutropenia, with 6 cases (9.5%) developed febrile neutropenia. 30 cases (47.6%) had toxic reactions in the digestive system, and 3 case (4.3%) had grade 3 liver dysfunction. 27 cases (42.8%) had skin and mucosal toxicity. 9 cases (14.3%) had mild fluid retention. No blood and digestive toxicity were observed in the ADT group. 33 cases (52.4%) and 48 (53.3%) of the two groups had symptoms of afternoon hot flashes and fatigue, (P = 0.961). CONCLUSION: Docetaxel chemotherapy combined with endocrine therapy could be one of effective treatments for delaying castration resistance of HVD-mHSPC, which could prolong PFS effectively and obtain a higher PSA response rate, high safety under close monitoring, and controllable adverse reactions.

Exosomal LINC01213 Plays a Role in the Transition of Androgen-Dependent Prostate Cancer Cells into Androgen-Independent Manners.

Background: Castration-resistant prostate cancer (CRPC), one of the prostate cancers, is a medical conundrum around the world. Some studies have demonstrated that many long noncoding RNAs in exosomes are very important in many types of cancer, including prostate cancer. However, until now, the function of exosomes in the occurrence and development of CRPC has not been reported. Methods: In vitro, cell coculture was used in LNCap cells and PC-3 cells, while the isolation and purification of exosomes and the subsequent treatment assays were used in functional studies. In vitro assays were performed to detect the transformation of ADPC cells (androgen-dependent prostate cancer) into AIPC cells (androgen-independent prostate cancer). Subsequently, a lncRNA-sequencing assay was performed to detect different lncRNA expression profiles in ADPC cells cocultured with or without AIPC exosomes. The role of LINC01213 was analysed by a TCGA database after silencing the expression of LINC01213. CCK-8, qRT-PCR, and Western blotting studies were performed to analyse the possible mechanism by which exosomes participate in prostate cancer progression. Results: In the coculture system, ADPC cells acquired androgen deprivation tolerance through exosome-mediated intercellular communication. Exosomes secreted by AIPC cells can promote the transformation of ADPC cells into androgen-independent cells in vitro and in vivo. lncRNA sequencing showed that LINC01213 was upregulated in exosomes derived from AIPC cell lines. The rescue experiments were preformed, and the results revealed that most of the functions of LINC01213 were performed by Wnt/ß-catenin. Conclusions: All the findings showed that exosomes play a key role in CRPC progression by upregulating LINC01213 and activating Wnt/ß-catenin signalling.

Denonvilliers' fascia acts as the fulcrum and hammock for continence after radical prostatectomy.

BACKGROUND: Radical prostatectomy (RP) is the primary treatment of localized prostate cancer. Immediate urinary incontinence post-RP was still common and depressing without specific reason. METHODS: A multicenter cohort of 154 consecutive patients from 2018 to 2020, who was diagnosed with localized prostate cancer underwent either modified mini-incision retropubic radical prostatectomy (Mmi-RRP) or laparoscopic radical prostatectomy (LRP) or robotic-assisted radical prostatectomy (RARP). Seventy-two patients with Denonvilliers' fascia (DF) spared were included in DFS (Denonvilliers' fascia sparing) group. Whereas eighty-two patients with DF completely or partially dissected were set as Group Control. The primary outcome was immediate continence (ImC). Continuous data and categorical data were analyzed with t-test and Chi-square test, respectively. Odds ratios (ORs) were calculated with logistic regression. RESULTS: Urinary continence of Group DFS was significantly better than that of Group Control at each time point within one year after operation. Incidence rate of continence in Group DFS and Group Control were 83.3% vs 13.4% (P < 0.01) for ImC, 90.3% vs 30.5% (P < 0.01) at 3 months, 91.7% vs 64.6% (P < 0.01) at 6 months, and 93.1% vs 80.5% (P = 0.02) at 1 year after operation, respectively. Positive surgical margin (PSM) showed no significant difference (20.8% vs 20.7%, P = 1.0). In multivariate analysis, DFS showed importance for ImC post RP (OR = 26.4, P < 0.01). CONCLUSIONS: Denonvilliers' fascia acted as the fulcrum and hammock for continence post RP. Preservation of DF contributed to better continence after RP without increase of PSM. Trail registration Our research was conducted retrospectively and approved by the ethical committees of Minhang Hospital, but not registered.

Significance of the prostate central gland and total gland volume ratio in the diagnosis of prostate cancer patients in the prostate specific antigen grey zone.

OBJECTIVE: To explore the significance of the prostate central gland to total gland volume ratio (PVc/PV) in the diagnosis of prostate cancer (PCa) in patients with prostate specific antigen (PSA) levels in the grey zone (4-10 ng/ml). METHODS: This retrospective study enrolled patients that had undergone prostate biopsy. The volume of the prostate and the central prostate gland were measured. The differences in PSA, the ratio of free to total PSA (f/tPSA), PSA density (PSAD) and PVc/PV between the PCa and non-PCa groups were compared. Receiver operating characteristic curve analysis for PCa and clinically significant PCa (csPCa) diagnosis were calculated according to PSA (reference), f/tPSA, PSAD and PVc/PV. RESULTS: This study enrolled 136 patients. There was no significant difference in PSA and f/tPSA between the PCa and non-PCa groups, while there were significant differences in PSAD and PVc/PV. The area under the curve values of PVc/PV for PCa or csPCa diagnosis were 0.876 and 0.933, respectively; and for PSAD, they were 0.705 and 0.790, respectively. These were significantly different compared with the PSA curve, whereas f/tPSA showed no significant difference from the PSA curve. CONCLUSION: PVc/PV could be a predictor of PCa when PSA is between 4-10 ng/ml.

Cancer-associated fibroblasts promote cell proliferation and invasion via paracrine Wnt/IL1ß signaling pathway in human bladder cancer.

Bladder cancer (BC) is the most common urinary system malignancy worldwide. However, the molecular mechanisms underlying its progression remain largely unexplored. Accumulating evidence indicates that the cancer-associated fibroblasts (CAFs), major constituents of tumor stroma, play a key role in tumor development. Herein, we have successfully isolated CAFs and paired normal fibroblasts (NFs) from bladder cancer tissues. We observed that the conditional medium from bladder cancer (CM-CAF) could significantly enhance cell proliferation (p<0.01) and invasion capacity (p<0.01) of bladder cancer cell lines T24 and J82, compared to the conditional medium from NFs or 5637 cells (bladder epithelial cell control). We subsequently identified cytokine IL1ß is enriched in CM-CAF, and a further functional study showed CAF-derived IL1ß contributes to the aggressiveness of T24 cells. In mechanisms, we demonstrated that a high level of IL1ß is capable of activating Wnt signaling in T24 cells, and Wnt signaling upregulates the expression of IL1ß, therefore forming a paracrine Wnt/IL1ß signaling feedback to enhance the aggressive phenotype of bladder cancer cells. In addition, we treated T24 cells with CM-CAF alone, or together with Wnt signaling inhibitor XAV939. We found that the inhibition of Wnt signaling could sufficiently abolish the oncogenic effect of CAFs on bladder cancer. In conclusion, our data revealed a novel mechanism that CAFs promote cell proliferation and invasion of human BC cells through Wnt/IL1ß signaling feedback. Inhibition of the Wnt signaling pathway may provide a promising target to block the interaction between CAF and bladder cancer cells.

Primary rhabdomyosarcoma of tunica vaginalis misdiagnosing as hydrocele: A case report and literature review.

Primary rhabdomyosarcoma of tunica vaginalis is very rare. We report a case of a 15-year-old man presenting as hydrocele. Pre-operatively, no masses were detected by ultrasonography. Hydrocelectomy was performed. At surgery, a 0.8 cm polypoid nodule and diffusely thickened tunica were found. Pathologic examination finally revealed rhabdomyosarcoma. A PET-CT was then performed and indicated scrotal implantation metastasis. The patient underwent radical inguinal orchiectomy and was treated with chemotherapy and radiotherapy after surgery. At 12 months of follow-up, he remained disease-free.

Long non-coding RNA-NEAT1, a sponge for miR-98-5p, promotes expression of oncogene HMGA2 in prostate cancer.

Increasing evidence demonstrated that noncoding RNAs (lncRNA, miRNA) play important roles in the cancer development. LncRNA NEAT1 functions as an oncogene in many cancers. However, the roles of NEAT1 in prostate cancer (PCa) remain largely unknown. In the present study, we aim to explore the molecular mechanism of NEAT1 in the development of PCa. We detected the expression levels of NEAT1 in a total of 16 benign prostatic hyperplasia tissues (BPH), 30 matched adjacent healthy control (HC) tissues and 30 PCa tissues, as well as PCa cell lines PC-3, DU-145, LNCaP and normal prostate epithelial cell line RWPE-1. The results showed that NEAT1 was significantly up-regulated in PCa tissues and PCa cell lines. Knockdown of NEAT1 can largely inhibit DU-145 and PC-3 cell growth and invasion. Bioinformatics analysis predicted NEAT1 has the binding site of miR-98-5p which can bind to the 3'UTR of HMGA2. And the expression level of NEAT1 has a positive correlation with HMAG2, while negative correlation with miR-98-5p in PCa cells. In addition, luciference assay and RNA immunoprecipitation (RIP) assay confirmed that NEAT1 can function as a competing endogenous RNA (ceRNA) by sponging miR-98-5p to active HMGA2. Moreover, silencing of HMGA2 can decrease the proliferation ability of PCa cells. Taken together, NEAT1/miR-98-5p/HMGA2 pathway is involved in the development and progression of PCa. NEAT1 could be recommended as a prognostic biomarker and inhibition of NEAT1 expression may be a promising strategy for PCa therapy.

LncRNA UCA1 acts as a sponge of miR-204 to up-regulate CXCR4 expression and promote prostate cancer progression.

Prostate cancer (PCa) is a devastating malignant disease with a poor prognosis. The aim of current study is to investigate the role of lncRNA-urothelial carcinoma associated 1 (UCA1) in the progression of PCa. We evaluated the expression levels of UCA1 in a total of 16 benign prostatic hyperplasia tissues (BPH) and 40 PCa tissues, as well as PCa cells. The functional regulatory effects of UCA1 were investigated using a series of cell function approaches. Our data showed that UCA1 is frequently overexpressed in PCa tissues compared with BPH tissues (P<0.01). Moreover, the higher expression of UCA1 was observed in patients with Gleason score ≥8 (P<0.05). In consistent, we found the expression levels of UCA1 was higher in the PCa cell lines PC-3, LnCaP, and DU-145 than in the normal prostate epithelial cell line RWPE-1 (P<0.01). Functionally, we found knockdown of UCA1 in PC-3 significantly suppressed cell growth and invasion of PC-3, while overexpression of UCA1 in DU-145 cells promote cell growth and invasion. Mechanistically, UCA1 overexpression permitted activation of CXCR4 oncogenes through inhibition of miR-204 activity, as evidenced by the positive association of these two genes with UCA1 levels and inverse correlation with miR-204 expression in PCa tissues. Luciferase activity assay further confirmed the targetting relationship between UCA1 and miR-204, CXCR4, and miR-204. The up-regulation of UCA1 in PC-3 cells significantly impaired the inhibitory effect of miR-204 on CXCR4 expression. Taken together, our research revealed that UCA1 works as an oncogene by targetting miR-204. The UCA1-miR-204-CXCR4 regulatory network regulated the growth and metastasis of PCa, providing new insight in the management of patients with such malignancy.