Liquid-liquid phase separation-related genes associated with prognosis, tumor microenvironment characteristics, and tumor cell features in bladder cancer.

OBJECTIVE: This study aimed to explore the Liquid-liquid phase separation (LLPS)-related genes associated with the prognosis of bladder cancer (BCa) and assess the potential application of LLPS-related prognostic signature for predicting prognosis in BCa patients. METHODS: Clinical information and transcriptome data of BCa patients were extracted from the Cancer Genome Atlas-BLCA (TCGA-BLCA) database and the GSE13507 database. Furthermore, 108 BCa patients who received treatment at our institution were subjected to a retrospective analysis. The least absolute shrinkage and selection operator (LASSO) analysis was performed to develop an LLPS-related prognostic signature for BCa. The CCK8, wound healing and Transwell assays were performed. RESULTS: Based on 62 differentially expressed LLPS-related genes (DELRGs), three DELRGs were screened by LASSO analysis including kallikrein-related peptidase 5 (KLK5), monoacylglycerol O-acyltransferase 2 (MOGAT2) and S100 calcium-binding protein A7 (S100A7). Based on three DELRGs, a novel LLPS-related prognostic signature was constructed for individualized prognosis assessment. Kaplan-Meier curve analyses showed that LLPS-related prognostic signature was significantly correlated with overall survival (OS) of BCa. ROC analyses demonstrated the LLPS-related prognostic signature performed well in predicting the prognosis of BCa patients in the training group (the area under the curve (AUC) = 0.733), which was externally verified in the validation cohort 1 (AUC = 0.794) and validation cohort 2 (AUC = 0.766). Further experiments demonstrated that inhibiting KLK5 could affect the proliferation, migration, and invasion of BCa cells. CONCLUSIONS: In this study, a novel LLPS-related prognostic signature was successfully developed and validated, demonstrating strong performance in predicting the prognosis of BCa patients.

Magnetic resonance imaging-based radiomics nomogram for the evaluation of therapeutic responses to neoadjuvant chemohormonal therapy in high-risk non-metastatic prostate cancer.

PURPOSE: The aim of this study was to assess the potential application of a radiomics features-based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa). METHODS: Clinicopathologic information was retrospectively collected from 162 patients with high-risk non-metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors. RESULTS: Sixty-three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754-0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739-0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839-0.954). The Hosmer-Lemeshow goodness-of-fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan-Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa. CONCLUSION: The radiomics-clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high-risk non-metastatic PCa.

Environmental explanation of prostate cancer progression based on the comprehensive analysis of polychlorinated biphenyls.

OBJECTIVE: Polychlorinated biphenyls (PCBs) have caused great environmental concerns. The study aims to investigate underlying molecular mechanisms between PCBs exposure and prostate cancer (PCa). METHODS: To investigate the association between PCBs exposure and prostate cancer by using CTD, TCGA, and GEO datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore pathways associated with PCBs-related genes (PRGs). Using Lasso regression analysis, a novel PCBs-related prognostic model was developed. Both internal and external validations were conducted to assess the model's validity. Molecular docking was utilized to assess the binding capacity of PCBs to crucial genes. At last, preliminary experimental validations were conducted to confirm the biological roles of Aroclor 1254 in PCa cells. RESULTS: The GO enrichment analysis of PRGs revealed that the biological processes were most enriched in the regulation of transcription from the RNA polymerase II promoter and signal transduction. The KEGG enrichment analysis showed that of the pathways in cancer is the most significantly enriched. Next, a PCBs-related model was constructed. In the training, test, GSE70770, and GSE116918 cohorts, the biochemical recurrences free survival of the patients with high-risk scores was considerably lower. The AUCs at 5 years were 0.691, 0.718, 0.714, and 0.672 in the four cohorts, demonstrating the modest predictive ability. A nomogram that incorporated clinical characteristics was constructed. The results of the anti-cancer drug sensitivity analysis show chemotherapy might be more beneficial for patients at low risk. The molecular docking analysis demonstrated PCBs' ability to bind to crucial genes. PCa cells exposed to Aroclor 1254 at a concentration of 1 µM showed increased proliferation and invasion capabilities. CONCLUSIONS: This study provides new insights into the function of PCBs in PCa and accentuates the need for deeper exploration into the mechanistic links between PCBs exposure and PCa progression.

A Novel Classification System of Renal Hilar Tumors for Surgical Guidance: Technique, Outcome, and Safety.

BACKGROUND: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors. METHODS: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups. RESULTS: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020). CONCLUSIONS: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.

Fatty acid metabolism-related molecular subtypes and a novel model for predicting prognosis in bladder cancer patients.

This study aims to develop fatty acid metabolism-related molecular subtypes and construct a fatty acid metabolism-related novel model for bladder cancer (BCa) by bioinformatic profiling. Genome RNA-seq expression data of BCa samples from the TCGA database and GEO database were downloaded. We then conducted consensus clustering analysis to identify fatty acid metabolism-related molecular subtypes for BCa. Univariate and multivariate Cox regression analysis were performed to identify a novel prognostic fatty acid metabolism-related prognostic model for BCa. Finally, we identified a total of three fatty acid metabolismrelated molecular subtypes for BCa. These three molecular subtypes have significantly different clinical characteristics, PD-L1 expression levels, and tumor microenvironments. Also, we developed a novel fatty acid metabolism-related prognostic model. Patients with low-risk score have significantly preferable overall survival compared with those with high-risk score in the training, testing, and validating cohorts. The area under the ROC curve (AUC) for overall survival prediction was 0.746, 0.681, and 0.680 in the training, testing and validating cohorts, respectively. This model was mainly suitable for male, older, high-grade, cluster 2-3, any TCGA stage, any N-stage, and any T-stage patients. Besides, we selected FASN as a hub gene for BCa and further qRT-PCR validation was successfully conducted. In conclusion, we developed and successfully validated a novel fatty acid metabolism-related prognostic model for predicting outcome for BCa patients.

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study

ABSTRACT Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Exploring Novel Genome Instability-associated lncRNAs and their Potential Function in Pan-Renal Cell Carcinoma.

OBJECTIVE: Genomic instability can drive clonal evolution, continuous modification of tumor genomes, and tumor genomic heterogeneity. The molecular mechanism of genomic instability still needs further investigation. This study aims to identify novel genome instabilityassociated lncRNAs (GI-lncRNAs) and investigate the role of genome instability in pan-Renal cell carcinoma (RCC). MATERIALS AND METHODS: A mutator hypothesis was employed, combining the TCGA database of somatic mutation (SM) information, to identify GI-lncRNAs. Subsequently, a training cohort (n = 442) and a testing cohort (n = 439) were formed by randomly dividing all RCC patients. Based on the training cohort dataset, a multivariate Cox regression analysis lncRNAs risk model was created. Further validations were performed in the testing cohort, TCGA cohort, and different RCC subtypes. To confirm the relative expression levels of lncRNAs in HK-2, 786-O, and 769-P cells, qPCR was carried out. Functional pathway enrichment analyses were performed for further investigation. RESULTS: A total of 170 novel GI-lncRNAs were identified. The lncRNA prognostic risk model was constructed based on LINC00460, AC073218.1, AC010789.1, and COLCA1. This risk model successfully differentiated patients into distinct risk groups with significantly different clinical outcomes. The model was further validated in multiple independent patient cohorts. Additionally, functional and pathway enrichment analyses revealed that GI-lncRNAs play a crucial role in GI. Furthermore, the assessments of immune response, drug sensitivity, and cancer stemness revealed a significant relationship between GI-lncRNAs and tumor microenvironment infiltration, mutational burden, microsatellite instability, and drug resistance. CONCLUSIONS: In this study, we discovered four novel GI-lncRNAs and developed a novel signature that effectively predicted clinical outcomes in pan-RCC. The findings provide valuable insights for pan-RCC immunotherapy and shed light on potential underlying mechanisms.

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study.

OBJECTIVES: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. MATERIALS AND METHODS: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. RESULTS: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. CONCLUSIONS: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Head-to-head comparisons of 68Ga-PSMA-11 and 18F-FDG PET/CT in evaluating patients with upper tract urothelial carcinoma: a prospective pilot study.

PURPOSE: To prospectively compare the uptake of 68Ga-prostate specific membrane antigen (68Ga-PSMA)-11 and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in upper tract urothelial carcinoma (UTUC) and investigate the correlation between radiological parameters and pathological features of UTUC. METHODS: Clinicopathologic and imaging data were collected from 10 UTUC patients who underwent preoperative 68Ga-PSMA-11 and 18F-FDG PET/CT scans. The diagnostic capabilities of both imaging techniques were analyzed and compared in UTUC. Angiogenesis in the malignancies was assessed using Chalkley counting and the expression of folate hydrolase 1 (FOLH1) and glucose transporter 1 (GLUT1) in UTUC were evaluated in the surgical specimens. Double immunofluorescence staining of PSMA and CD34 was used to examine tumor neovascularization. Tracer uptake and expression were compared and explored. Additionally, 10 patients with clear cell renal cell carcinoma (ccRCC) were included for prospective, comparative research. RESULTS: Ten UTUC patients with 12 malignant lesions and another 10 ccRCC patients were included. 18F-FDG PET/CT demonstrated a more effective detection of UTUC foci compared to 68Ga-PSMA-11 PET/CT (the SUVmax of 18.48 ± 6.73 vs. 4.38 ± 1.45, P < 0.01). Immunohistochemical analysis revealed a statistically significant difference in the expression of PSMA and GLUT1 in UTUC (P = 0.048), with higher pathological grades showing more intense GLUT1 staining than PSMA (75% vs. 12.5%). The Chalkley counting of angiogenesis in ccRCC was significantly higher than that in UTUC (229.34 vs. 71.67), which was proportional to 68Ga-PSMA-11 PET/CT SUVmax (both P < 0.05). CONCLUSION: 18F-FDG PET/CT holds better clinical potential for evaluating UTUC and detecting lymph node metastasis compared to 68Ga-PSMA-11 PET/CT, likely due to the relatively scant expression of FOLH1 in tumor neovascular endothelium while the abundant expression of GLUT1 in malignancy. Furthermore, the lower neovascular density in UTUC should not be overlooked.

Integrative Analysis Developing and Validating Potential Candidate Biomarkers for Cancer Stemness Features of Pan-Renal Cell Carcinoma.

In our study, 49 key genes significantly associated with renal cell carcinoma (RCC) stemness were obtained. Next, we developed a molecular prognostic signature associated with stemness features of pan-RCC. The difference in overall survival (OS) between the high- and low-risk groups was statistically significant (p < .05). The area under the receiver operating characteristic curve for 1-year OS, 5-year OS, and 10-year OS was 0.759, 0.712, and 0.918, respectively. The results of validation in The Cancer Genome Atlas cohort and International Cancer Genome Consortium cohort revealed the predictive capability of this signature. Furthermore, we selected three genes and further validation showed that these three hub genes were potential hub biomarkers for pan-RCC stemness features.

Risk factors for lymphorrhea and lymphocele after radical prostatectomy: a retrospective case-control study.

PURPOSE: To investigate the risk factors for postoperative lymphorrhea or/and lymphocele (PLL) in patients undergoing radical prostatectomy (RP). MATERIALS AND METHODS: The clinical data of 606 patients were retrospectively collected. The receiver operating characteristic (ROC) curve was utilized to identify the optimal cutoff value. Multivariable logistic regression analysis was used to screen the independent predictors of PLL. RESULTS: Univariate analysis showed that nine factors differed between the PLL and non-PLL group. Multivariable logistic regression analysis showed that low preoperative fibrinogen level, extraperitoneal surgery, robot-assisted laparoscopic radical prostatectomy (RALRP), and hypoalbuminemia were risk factors and the use of fibrin glue was a protective factor. Correlation analysis showed that the scope of LN dissection (LND) and number of lymph nodes (LNs) dissected were positively correlated with PLL in the extraperitoneal approach, but were not significantly correlated with PLL in the transperitoneal approach. The use of fibrin glue was negatively associated with PLL in the overall procedure and the extraperitoneal approach, but not significantly so in the transperitoneal approach. Comparison of LNs clearance between the two surgical approaches revealed that the extent of LND and number of LNs dissected in the extraperitoneal approach were less than in the transperitoneal approach. CONCLUSION: During RALRP, more attention should be paid to fully clotting the broken end of lymphatic vessels. The use of fibrin glue could reduce the probability of PLL. The extent of LND or number of LNs dissected were positively correlated with PLL in the extraperitoneal approach.

ARPC1A correlates with poor prognosis in prostate cancer and is up-regulated by glutamine metabolism to promote tumor cell migration, invasion and cytoskeletal changes.

OBJECTIVE: This study aimed to identify potential biomarkers for prostate cancer (PCa) progression and metastasis, and to discern their biological functions. METHODS: Bioinformatics methods were used to screen for hub genes. The expression level of key hub genes in PCa was determined and their prognostic significance was examined. A series of functional assays were performed to investigate the function of the highest-ranking hub gene. RESULTS: Actin related protein 2/3 complex subunit 1A (ARPC1A) was identified as the hub gene. ARPC1A was highly expressed in PCa tissues and cell lines, and was an independent prognostic factor for predicting biochemical recurrence after radical prostatectomy and overall survival of PCa patients. Knockdown of ARPC1A inhibited PCa cell migration, invasion and cytoskeleton formation, but had no impact on cell proliferation and cell cycle progression. In vivo, ARPC1A overexpression promoted lung metastasis of PCa, but had no efffect on tumor growth. Additionally, glutamine metabolism was identified as an upstream regulator of ARPC1A, and promoted migration, invasion and cytoskeletal changes of PCa cell through ARPC1A. CONCLUSION: These findings suggested that ARPC1A, which correlates with poor prognosis in PCa, functions downstream of glutamine metabolism to regulate cytoskeletal changes, cellular migration and cellular invasion in this disease.

Head-to-head comparisons of [68Ga]Ga-PSMA-11 PET/CT, multiparametric MRI, and prostate-specific antigen for the evaluation of therapeutic responses to neoadjuvant chemohormonal therapy in high-risk non-metastatic prostate cancer patients: a prospective study.

PURPOSE: The optimal tool to evaluate the tumour therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa) remains uncertain. We compared the role of [68Ga]-labeled prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computerized tomography ([68Ga]Ga-PSMA-11 PET/CT), multiparametric MRI (mpMRI), and prostate-specific antigen (PSA) and assessed the practical value of the recent European Association of Urology and European Association of Nuclear Medicine (EAU/EANM) recommended criteria of PSMA PET/CT to evaluate the therapeutic responses to NCHT in patients with high-risk non-metastatic PCa. METHODS: This prospective study included 72 high-risk non-metastatic PCa patients receiving NCHT followed by radical prostatectomy from June 2021 to March 2022. PSA testing, [68Ga]Ga-PSMA-11 PET/CT, and mpMRI scanning were conducted in all patients before and after NCHT. Therapeutic responses to NCHT were evaluated with PSA, RECIST 1.1, PERCIST 1.0, and EAU/EANM recommended criteria. Postoperative pathological results were considered the reference standard. A favourable pathological response was defined as pathologic complete remission (pCR) or minimal residual disease (MRD). Diagnostic accuracy was assessed by sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa index. Logistic regression analysis was used to determine the independent predictive value of [68Ga]Ga-PSMA-11 PET/CT-derived parameters. RESULTS: All cases experienced a marked decrease in PSA levels after NCHT. Twenty-four (33.33%) cases experienced a favourable pathological response, including five (6.94%) cases of pCR and 19 (26.39%) cases of MRD. According to the results of [68Ga]Ga-PSMA-11 PET/CT, EAU/EANM recommended criteria indicated that 20 (27.78%) cases had a CR, whereas PERCIST 1.0 criteria indicated that 23 (31.94%) cases had a CR. There was a strong association between EAU/EANM recommended criteria and PERCIST 1.0 criteria (Pearson's R=0.857). The sensitivity (75.00%, 79.17% vs. 58.33%, 58.33%), specificity (95.83%, 91.67% vs. 83.33%, 68.75%), PLR (18.00, 9.50 vs. 3.50, 1.87), NLR (0.26, 0.23 vs. 0.50, 0.61), PPV (90.0%, 82.6% vs. 63.6%, 48.3%), and NPV (88.5%, 89.8% vs. 80.0%, 76.7%) of [68Ga]Ga-PSMA-11 PET/CT (including EAU/EANM recommended criteria and PERCIST 1.0 criteria) to predict favourable pathological responses were all superior to those of mpMRI and nadir PSA. The kappa index to predict a favourable pathological response was 0.257 for PSA, 0.426 for RECIST 1.1, 0.716 for PERCIST 1.0, and 0.739 for EAU/EANM recommended criteria. Multivariate logistic analysis revealed that the post-NCHT maximum standardized uptake value (SUVmax) before radical prostatectomy was an independent predictor of a favourable pathological response to NCHT. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT had a better concordance with a favourable pathological response to NCHT compared with nadir PSA and mpMRI. EAU/EANM recommended criteria and PERCIST 1.0 criteria performed equally to identify pathological responders when [68Ga]Ga-PSMA-11 PET/CT was used as a therapeutic response assessment tool.

Low TLR and PSMA-TV predict biochemical response to abiraterone acetate in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage.

OBJECTIVE: To explore whether 68Ga-PSMA-11 PET/CT-derived parameters could predict biochemical response to abiraterone acetate (AA) treatment and prognosis in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage. METHODS: The clinicopathologic data of 106 mCRPC cases receiving AA treatment were retrospectively analyzed. Logistic regression analysis was used to determine the independent predictors of biochemical response to AA treatment. Cox analyses were applied to investigate the independent prognostic factors for time to biochemical progression (TTBP) and radiological progression-free survival (rPFS). Survival analysis and ROC curve were also used. RESULTS: Multivariable Logistic analysis demonstrated that prior ADT duration ≥ 12 months, low prostate specific membrane antigen receptor-expressing tumor volume (PSMA-TV), low tumor to liver ratio (TLR) were independent predictors of biochemical response to AA treatment. Multivariate Cox analysis demonstrated that low PSMA-TV and low TLR were independent prognostic factors of longer TTBP and rPFS. The TTBP and rPFS of patients with higher PSMA-TV or TLR were significantly decreased compared with that of patients with lower PSMA-TV and TLR. The area under ROC curve (AUC) of combining ADT duration, PSMA-TV and TLR was 0.82 for predicting biochemical response to AA, which was significantly increased compared with that of other 68Ga-PSMA-11 PET/CT-derived parameters alone. CONCLUSIONS: Low PSMA-TV, low TLR were vital independent predictors of biochemical response to AA treatment and were associated with preferable prognosis in mCRPC patients. Combining ADT duration, PSMA-TV and TLR performed well in distinguishing AA responders from non-responders in mCRPC patients.

A Novel Tumor Mutation Burden Related lncRNA Signature Identified Prognosis and Tumor Immune Microenvironment Features in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Emerging evidence indicates that long noncoding RNA (lncRNA) plays an important biological role in clear cell renal cell carcinoma (ccRCC); however, the clinical value of tumor mutation burden-related lncRNA in ccRCC patients is unknown yet. METHODS: Somatic mutation profiles and lncRNA expression data of ccRCC were downloaded from the TCGA database. We retrospectively analyzed lncRNA expression data and survival information from 116 patients with ccRCC fromJanuary 2013 to January 2014. Univariate and multivariate Cox regression analyses were performed to construct lncRNA signature, and the prognosis value was determined by Kaplan-Mayer and receiver operating characteristic curve (ROC) analysis. RESULTS: Based on 160 differentially expressed TMB-related lncRNAs, two TMB-related molecular clusters with distinct immune checkpoints expression and immune cells infiltration were established for ccRCC patients. Moreover, a novel TMB-related lncRNA signature was constructed based on five lncRNAs for individualized prognosis assessment. High-risk group represents significantly worse overall survival in all cohorts. The area under the ROC curve was 0.716, 0.775 and 0.744 in the training cohort, testing cohort and TCGA cohort, respectively. Results of qRT-PCR successfully validated the expression levels of AP002360.3, LINC00460, AL590094.1, LINC00944 and LINC01843 in HK-2, 786-O, 769-P and ACHN cells. More importantly, the predictive performance of TMB-related lncRNA signature was successfully validated in an independent cohort of 116 ccRCC patients at our institution. CONCLUSION: This study successfully developed and validated a novel TMB-related lncRNA signature for individualized prognosis assessment of ccRCC patients.

Semantic Computed Tomography Features for Predicting BRCA1-associated Protein 1 and/or Tumor Protein p53 Gene Mutation Status in Clear Cell Renal Cell Carcinoma.

PURPOSE: The purpose of this study was to explore the semantic computed tomography (CT) features associated with BRCA1-associated protein 1 (BAP1) and/or tumor protein p53 (TP53) mutation in clear cell renal cell carcinoma (ccRCC). METHODS AND MATERIALS: Clinical characteristics and gene mutation information of 336 ccRCC patients were retrieved from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma database (TCGA-KIRC). Kaplan-Meier analysis was performed to examine prognosis by gene mutation. The CT imaging data and gene mutation information of 156 ccRCC patients treated between January 2019 and January 2021 (the training cohort) were retrospectively analyzed. The CT imaging information and gene mutation data of 123 patients with ccRCC were downloaded from The Cancer Imaging Archive and The Cancer Genome Atlas database (the external validation cohort). Univariate Chi-square test and multivariate binary logistic regression analysis were performed to determine predictors of gene mutation; a nomogram was developed using these predictors. Receiver operating characteristic curve analysis and the Hosmer-Lemeshow test were performed to evaluate the performance of the nomogram. RESULTS: Kaplan-Meier analysis showed that BAP1 and/or TP53 mutation was significantly correlated with worse survival outcome. Multivariate binary logistic regression analysis indicated ill-defined margin (P = .001), spiculated margin (P = .018), renal vein invasion (P = .002), and renal pelvis invasion (P = .001) were independent predictors of BAP1 and/or TP53 mutation. A nomogram containing these 4 semantic CT features was constructed; the area under the receiver operating characteristic curves was 0.872 (95% CI, 0.809-0.920). The Hosmer-Lemeshow test showed acceptable goodness-of-fit for the nomogram (X2 = 1.194, P = .742). The nomogram was validated in the validation cohort; it showed good accuracy (area under the receiving operating characteristic curve = 0.819, 95% CI, 0.740-0.883) and was well calibrated (X2 = 3.934, P = .559). CONCLUSIONS: Semantic CT features are a potential and promising method for predicting BAP1 and/or TP53 mutation status in ccRCC patients.

[Influence of prostatic calculi on the results of prostate biopsy in patients with a PSA level of 4－10 µg/L].

OBJECTIVE: To investigate the influence of prostatic calculi on the results of prostate biopsy in patients with a PSA level of 4－10 µg/L. METHODS: We reviewed the clinical data on 317 patients with a PSA level of 4－10 µg/L on prostate biopsy performed in The First Affiliated Hospital of Fujian Medical University between May 2012 and May 2019, concerning age, body mass index (BMI), prostate volume, PSA level, FPSA/TPSA ratio, PSA density (PSAD), scores on Prostate Imaging Reporting and Data System version 2 (PI-RADS), prostatic calculi and pathological findings. Using logistic regression analysis and ROC curves, we evaluated the influence of prostatic calculi on the results of prostate biopsy. RESULTS: Multivariate analysis showed that age and the PI-RADS score were independent risk factors of positive prostate biopsy, while the prostate volume, FPSA/TPSA ratio and calculus burden were independent protective factors, and that the PI-RADS score was an independent risk factor of clinically significant PCa, while calculus burden and FPSA/TPSA ratio were independent protective factors. Subgroup analysis of the prostatic calculi revealed that the rates of positive prostate biopsy and clinically significant PCa were higher in the patients with calculi in the peripheral zone than in the other groups, but lower in those with calculi in the central or transitional zone than in the peripheral zone and non-calculus groups. CONCLUSIONS: The rates of positive prostate biopsy and clinically significant PCa are low in prostatic calculus patients with a PSA level of 4－10 µg/L, especially in those with calculi in the central or transitional zone.

Angiogenesis-Related Molecular Subtypes and a Novel Prognostic Signature in Clear Cell Renal Cell Carcinoma Patients.

BACKGROUND: This study aimed to develop and validate a novel angiogenesis-related gene (ARG) signature and molecular subtypes by bioinformatics analysis. MATERIALS AND METHODS: The transcriptome data and clinical data were obtained from TCGA and ICGC database. We performed consensus clustering analysis to identify angiogenesis molecular subtypes for ccRCC. Univariate and multivariate Cox regression analyses were used to develop a novel ARG-related signature as a prognostic biomarker for ccRCC. Internal and external validation were then performed in TCGA and ICGC cohort, respectively. RESULTS: We identified a total of two angiogenesis molecular subtypes of ccRCC. The overall survival (OS) of subtype 1 ccRCC was significantly decreased compared with that of subtype 2 ccRCC (P=0.001). These two molecular subtypes have significantly different tumor microenvironment and immune checkpoint inhibitor sensitivities (P<0.05). Besides, we developed a novel signature based on three ARGs (including MSX1, TIMP1 and JAG2) for subtype 1 ccRCC. The difference in OS between high- and low-risk group was statistically significant in training cohort (P=0.009), test cohort (P=0.024), the whole type 1 cohort (P<0.001), and validation cohort (P=0.041). The AUC for one-year OS prediction was 0.732, 0.710, 0.725, and 0.645 in training cohort, test cohort, the whole type 1 cohort, and validation cohort, respectively. Independent prognostic analysis showed that this signature was an independent predictor for OS of subtype 1 ccRCC (P=0.028914). The power of this prognostic signature was superior to other signatures reported in previous studies. CONCLUSION: We developed and successfully validated a novel ARG signature for predicting prognosis of subtype 1 ccRCC, which was superior to several previous signatures.