Advantage of whole-mount histopathology in prostate cancer: current applications and future prospects.

BACKGROUND: Whole-mount histopathology (WMH) has been a powerful tool to investigate the characteristics of prostate cancer. However, the latest advancement of WMH was yet under summarization. In this review, we offer a comprehensive exposition of current research utilizing WMH in diagnosing and treating prostate cancer (PCa), and summarize the clinical advantages of WMH and outlines potential on future prospects. METHODS: An extensive PubMed search was conducted until February 26, 2023, with the search term "prostate", "whole-mount", "large format histology", which was limited to the last 4 years. Publications included were restricted to those in English. Other papers were also cited to contribute a better understanding. RESULTS: WMH exhibits an enhanced legibility for pathologists, which improved the efficacy of pathologic examination and provide educational value. It simplifies the histopathological registration with medical images, which serves as a convincing reference standard for imaging indicator investigation and medical image-based artificial intelligence (AI). Additionally, WMH provides comprehensive histopathological information for tumor volume estimation, post-treatment evaluation, and provides direct pathological data for AI readers. It also offers complete spatial context for the location estimation of both intraprostatic and extraprostatic cancerous region. CONCLUSIONS: WMH provides unique benefits in several aspects of clinical diagnosis and treatment of PCa. The utilization of WMH technique facilitates the development and refinement of various clinical technologies. We believe that WMH will play an important role in future clinical applications.

Targeting SMYD2 inhibits prostate cancer cell growth by regulating c-Myc signaling.

SMYD2 is a lysine histone methyl transferase involved in various cancers epigenetically via methylating histone H3K4, and H3K36. c-Myc is one of the major drivers of prostate cancer (PCa) initiation and progression. The roles of SMYD2 in PCa and the regulators of c-Myc activity in PCa are still under-researched. SMYD2 expression and survival outcomes in PCa cohorts were analyzed by bioinformatics analysis. SMYD2 protein levels were detected in PCa tissues by immunohistochemistry. SMYD2 knockdown cells were established to identify the effects of SMYD2 on cell growth in vitro and in vivo. GSEA and RNA sequencing were adopted to reconnoiter the signaling regulated by SMYD2 in PCa. The relationship between SMYD2 and c-Myc was examined by western blot analysis, qPCR, and immunohistochemistry. SMYD2 specific inhibitor-AZ505 was used to pharmacologically inhibit SMYD2 function in vitro and in vivo. SMYD2 expression increased in PCa tissues compared with benign prostate tissues and higher SMYD2 expression was associated with a higher risk of biochemical relapse after radical prostatectomy. SMYD2 knockdown inhibited the growth of PCa cells both in vitro and in vivo. Furthermore, high SMYD2 levels conduced to activated c-Myc signaling in PCa cells. Importantly, the pharmacological intervention of SMYD2 by AZ505 significantly repressed PCa cell growth both in vitro and in vivo. Our findings indicate that SMYD2 inhibition restrains PCa cell proliferation by regulating c-Myc signaling and provide evidence for the potential practice of SMYD2 targeting in the treatment of PCa.

Construction of a robust prognostic model for adult adrenocortical carcinoma: Results from bioinformatics and real-world data.

This study aims to construct a robust prognostic model for adult adrenocortical carcinoma (ACC) by large-scale multiomics analysis and real-world data. The RPPA data, gene expression profiles and clinical information of adult ACC patients were obtained from The Cancer Proteome Atlas (TCPA), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Integrated prognosis-related proteins (IPRPs) model was constructed. Immunohistochemistry was used to validate the prognostic value of the IPRPs model in Fudan University Shanghai Cancer Center (FUSCC) cohort. 76 ACC cases from TCGA and 22 ACC cases from GSE10927 in NCBI's GEO database with full data for clinical information and gene expression were utilized to validate the effectiveness of the IPRPs model. Higher FASN (P = .039), FIBRONECTIN (P < .001), TFRC (P < .001), TSC1 (P < .001) expression indicated significantly worse overall survival for adult ACC patients. Risk assessment suggested significantly a strong predictive capacity of IPRPs model for poor overall survival (P < .05). IPRPs model showed a little stronger ability for predicting prognosis than Ki-67 protein in FUSCC cohort (P = .003, HR = 3.947; P = .005, HR = 3.787). In external validation of IPRPs model using gene expression data, IPRPs model showed strong ability for predicting prognosis in TCGA cohort (P = .005, HR = 3.061) and it exhibited best ability for predicting prognosis in GSE10927 cohort (P = .0898, HR = 2.318). This research constructed IPRPs model for predicting adult ACC patients' prognosis using proteomic data, gene expression data and real-world data and this prognostic model showed stronger predictive value than other biomarkers (Ki-67, Beta-catenin, etc) in multi-cohorts.

Identification of a methylation panel aid in risk stratification in node-positive penile squamous cell carcinoma.

Molecular prognostic factors for individualized treatment of squamous cell carcinoma (SCC) are poorly defined. Our study developed and validated a novel molecular tools aid in preinguinal and postinguinal lymphadenectomy risk stratification in node-positive penile SCC. Patients with node-positive penile SCC who underwent inguinal or ilioinguinal lymphadenectomy were divided into three cohorts: a discovery set, a development set and a validation set. The local ethics committee approved the study. The primary endpoint was cancer-specific survival (CSS). At the discovery stage, 17 CpG sites were significantly associated with CSS. In the development set, we constructed a 3-CpG-based prognostic score for survival prediction. The hazard ratio (HR) of the panel (dichotomized using the optimal cutoff) was 5.8 in the multivariate analyses (P < .001). The addition of the methylation score significantly improved the pN-stage C-index from 0.70 to 0.79 (incremental C = 0.09, P < .001). In the validation set, the methylation panel showed a HR of 9.9 in the multivariate analyses. The addition of the molecular marker improved the pN-stage C-index from 0.69 to 0.78 (incremental C = 0.09, P < .001). The methylation score remarkably separated survival curves in different pN stages, which indicate that the tool can be applied to tailor the treatment in both preinguinal and postinguinal lymphadenectomy settings. We developed and validated a prognostic methylation panel for node-positive penile SCC. The tool may aid in the risk stratification of the population with heterogeneous outcomes and needs prospective validation. Patients in high-risk group may benefit from more aggressive therapy or clinical trials.

Inherited Mutations in Chinese Men With Prostate Cancer.

BACKGROUND: Although China accounts for 7.8% of worldwide new prostate cancer (PCa) cases and 14.5% of new deaths according to GLOBOCAN 2020, the risk of PCa associated with germline mutations is poorly defined, hampered in part by lack of nationwide evidence. Here, we sequenced 19 PCa predisposition genes in 1,836 Chinese patients with PCa and estimated disease risk associated with inherited mutations. PATIENTS AND METHODS: Patients were recruited from 4 tertiary cancer centers (n=1,160) and a commercial laboratory (n=676). Germline DNA was sequenced using a multigene panel, and pathogenic/likely pathogenic (P/LP) mutation frequencies in patients with PCa were compared with populations from the gnomAD (Genome Aggregation Database) and ChinaMAP (China Metabolic Analytics Project) databases. Clinical characteristics and progression-free survival were assessed by mutation status. RESULTS: Of 1,160 patients from hospitals, 89.7% had Gleason scores ≥8, and 65.6% had metastases. P/LP mutations were identified in 8.49% of Chinese patients with PCa. Association with PCa risk was significant for mutations in ATM (odds ratio [OR], 5.9; 95% CI, 3.1-11.1), BRCA2 (OR, 15.3; 95% CI, 10.0-23.2), MSH2 (OR, 15.8; 95% CI, 4.2-59.6), and PALB2 (OR, 5.9; 95% CI, 2.7-13.2). Compared with those without mutations, patients with mutations in ATM, BRCA2, MSH2, or PALB2 showed a poor outcome with treatment using androgen deprivation therapy and abiraterone (hazard ratio, 2.19 [95% CI, 1.34-3.58] and 2.47 [95% CI, 1.23-4.96], respectively) but similar benefit from docetaxel. CONCLUSIONS: The present multicenter study confirmed that a significant proportion of Chinese patients with PCa had inherited mutations and identified predisposition genes in this underreported ethnicity. These data provide empirical evidence for precision prevention and prognostic estimation in Chinese patients with PCa.

Targeting CPT1B as a potential therapeutic strategy in castration-resistant and enzalutamide-resistant prostate cancer.

BACKGROUND: Prostate cancer is characterized by aberrant lipid metabolism, including elevated fatty acid oxidation. Carnitine palmitoyltransferase 1B (CPT1B) catalyzes the rate-limiting step of fatty acid oxidation. This study aimed to determine if CPT1B has a critical role in prostate cancer progression and to identify its regulatory mechanism. METHODS: CPT1B expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases was compared with patient survival data. A tissue microarray was constructed with 60 samples of prostate cancer and immunohistochemically stained for CPT1B. Castration-resistant prostate cancer (CRPC) cell lines 22RV1 and C4-2 in which CPT1B expression had been stably knocked down were established; and cell proliferation, cell cycle distribution, and invasion were investigated by Cell Counting Kit-8 (CCK-8) and colony formation assays, flow cytometry, and Transwell assays, respectively. To examine the impact of androgen receptor (AR) inhibition on CPT1B expression, JASPAR CORE was searched to identify AR-binding sites in CPT1B. Dual luciferase and ChIP assays were performed to confirm CPT1B activity and AR binding, respectively. Differentially expressed genes (DEGs) in prostate cancer underwent gene set enrichment analysis (GSEA). Enzalutamide-resistant C4-2 cells were generated and the mechanism of enzalutamide resistance and downstream signaling pathway changes of CPT1B to C4-2 was explored through CCK-8 test. RESULTS: CPT1B expression was upregulated in human prostate cancer compared with normal prostate tissue and was associated with poor disease-free survival and overall survival. Silencing of CPT1B resulted in downregulated cell proliferation, reduced S-phase distribution, and lower invasive ability, whereas the opposite was observed in CRPC cells overexpressing CPTB1. DEGS in prostate cancer were correlated with G-protein-coupled receptor signaling, molecular transducer activity, and calcium ion binding. AR may regulate CPT1B expression and activity via specific binding sites, as confirmed by dual luciferase and ChIP assays. The CCK-8 experiment demonstrated that CPT1B overexpression in C4-2 cells did not significantly increase the ability of enzalutamide resistance. However, overexpression of CPT1B in C4-2R cells significantly increased the enzalutamide resistance. Upregulation of CPT1B expression increased AKT expression and phosphorylation. CONCLUSIONS: CPT1B is upregulated in prostate cancer and is correlated with poor prognosis, indicating its potential as a biomarker. AR inhibits the transcription of CPT1B. In the CRPC cell line, overexpression of CPT1B alone cannot promote enzalutamide resistance, but in the drug-resistant line C4-2R, overexpression of CPT1B can promote the resistance of C4-2R to enzalutamide.

Prognosis of the 8th TNM Staging System for Penile Cancer and Refinement of Prognostication by Incorporating High Risk Human Papillomavirus Status.

PURPOSE: We evaluated the prognostic value of the 8th TNM staging system and assessed a modified N stage incorporating high risk human papillomavirus status in a multicenter cohort. MATERIALS AND METHODS: Included in analysis were 292 patients with M0 penile squamous cell carcinoma from a total of 6 referral centers. High risk human papillomavirus status was examined. The Chinese multicenter cohort of 230 patients was used to validate the 8th TNM staging system and propose a modified N classification. The modified classification was further validated in an independent cohort of 62 patients at Moffitt Cancer Center. RESULTS: Median followup was 48.9 months. Of the patients 42% had node positive disease. In the primary cohort the 8th TNM staging system achieved better discriminative ability compared with the 7th edition (C-index 0.769 vs 0.751, p=0.029). The 8th N category better stratified survival between pN1 and pN2 (p <0.001) and reclassified 15% of node positive cases into pN1 with 64% 5-year overall survival. High risk human papillomavirus status further stratified pN2-3 disease (p=0.040) and pN2-3 high risk human papillomavirus negative status was associated with 32% 5-year survival. The newly proposed 3-tier classification (1-pN1, 2-pN2-3 high risk human papillomavirus positive and 3-pN2-3 high risk human papillomavirus negative) significantly increased the C-index from 0.620 to 0.666 compared with the 8th N classification of pN1 and pN2-3 (p=0.04). In the external validation cohort significantly improved results were observed using the modified N classification (C-index 0.567-0.641, p=0.027). CONCLUSIONS: The 8th edition of the AJCC (American Joint Committee on Cancer) Staging System for penile cancer showed better discriminative ability for prognostic stratification. Adding high risk human papillomavirus status further improved the prognostic stratification in patients with node positive disease.

Conditional Survival in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab.

BACKGROUND Nivolumab is approved for the treatment of advanced renal cell carcinoma (RCC). However, traditional overall survival (OS) or progression-free survival (PFS) do not reflect patient prognosis after initial management. Therefore, this study aimed to evaluate conditional overall survival (COS) and conditional progression-free survival (CPFS) in patients with advanced RCC treated with nivolumab. MATERIAL AND METHODS There were 847 patients with advanced RCC treated with first-line nivolumab plus ipilimumab (n=425) and sunitinib (n=422), and 821 patients were treated with second-line nivolumab (n=410) and everolimus (n=411). Primary endpoints were COS and CPFS. Individual patient data of PFS and OS were digitally reconstructed from two large randomized controlled trials (CheckMate 025 and CheckMate 214). RESULTS In first-line treatment, compared with sunitinib, improvement of one-year CPFS for the nivolumab plus ipilimumab group after living for 0.5 and 0.75 years were 14% (from 53.0% to 67.0%) and 16% (from 57.0% to 73.0%) higher than the one-year PFS of 6.5% (from 42.9% to 49.4%), with similar results for one-year COS following first-line treatment. For second-line treatment, compared with everolimus, the improvement of one-year CPFS for the nivolumab group after living for 0.5 and 0.75 years were 19% (from 25.0% to 44.0%) and 19% (from 27.0% to 46.0%) and significantly higher than the one-year PFS of 4.5% (from 18.5% to 23.0%). CONCLUSIONS Survival benefit for patients with advanced RCC from nivolumab (plus ipilimumab) compared with sunitinib was more evident from conditional survival (CS) analysis of first-line treatment.

The Role of Serine Peptidase Inhibitor Kazal Type 13 (SPINK13) as a Clinicopathological and Prognostic Biomarker in Patients with Clear Cell Renal Cell Carcinoma.

BACKGROUND The serine peptidase inhibitor Kazal type 13 (SPINK13) gene has tumor suppressor activity, but its role in renal cell carcinoma (RCC) remains unknown. This study aimed to investigate mRNA expression of SPINK13 in clear cell renal cell carcinoma (CCRCC) in human tissue and to use bioinformatics data to investigate the role of SPINK13 expression as a clinicopathological and prognostic biomarker for patients with CCRCC. MATERIAL AND METHODS Patients with CCRCC (N=533) with available RNA sequence data from The Cancer Genome Atlas (TCGA)-CCRCC database were analyzed with patients who had a tissue diagnosis of CCRCC (N=305) at the Fudan University Shanghai Cancer Center (FUSCC). Differential transcriptional and proteome expression profiles were obtained from the ONCOMINE cancer microarray database, TCGA, and the Human Protein Atlas (HPA) database. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) measured SPINK13 mRNA expression in 305 samples of CCRCC tissue from the FUSCC. The effects of clinicopathological parameters on progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier and log-rank test. RESULTS Transcriptional and proteome expression of SPINK13 were significantly increased CCRCC tissue samples. Increased SPINK13 mRNA expression was significantly associated with reduced PFS and OS in 838 patients with CCRCC patients from the two independent cohorts, the FUSCC and the TCGA-CCRCC cohorts (p<0.01). Gene set enrichment analysis (GSEA) showed that SPINK13 expression was involved in complement, apical junction, epithelial-mesenchymal transition (EMT), glycolysis, hypoxia, and inflammation signaling pathways. CONCLUSIONS Increased expression of SPINK13 was associated with poor prognosis in patients with CCRCC.

Prognostic significance of the dynamic changes of systemic inflammatory response in metastatic renal cell carcinoma.

PURPOSE: To elucidate the prognostic value of systemic inflammatory response in patients with metastatic renal cell carcinoma (mRCC) who are treated with sunitinib, we evaluated the prognostic role of C-reactive protein (CRP) kinetics. This study also compared prognostic models containing CRP kinetics and neutrophil-to-lymphocyte ratio (NLR) kinetics. MATERIALS AND METHODS: A consecutive cohort of 94 patients with mRCC who were treated with sunitinib was retrospectively included from Fudan University Shanghai Cancer Center. According to dynamic changes in CRP and the NLR, patients were divided into three groups for analysis of CRP and NLR kinetics. The associations between survival and potential prognostic factors were assessed. The incremental value of prognostication was evaluated. RESULTS: A significant difference (P<0.001) in overall survival (OS) was observed among the three groups of CRP kinetics. The median OS of the non-elevated group was nearly 1.3-fold longer than that of the normalized group (33.0 vs. 26.3 months), and two times longer than that of the non-normalized group (33.0 vs. 14.0 months). Multivariate analysis showed that CRP and NLR kinetics were independent prognostic indicators. The model containing CRP kinetics had a better predictive accuracy than that with NLR kinetics, which was supported by the C-index (0.731 vs. 0.684) and the likelihood ratio χ² test (79.9% vs. 44.9%). CONCLUSION: Our study suggests that dynamic changes in CRP can better predict survival in patients with mRCC who are treated with sunitinib. Routine assessment of CRP before and after targeted therapy would help identify patients at risk of a poor outcome.

Functional variants in the low-density lipoprotein receptor gene are associated with clear cell renal cell carcinoma susceptibility.

Recent studies indicate that abnormal levels of low-density lipoprotein (LDL), which is an important component of dyslipidaemia, are associated with alterations to cancer risk, including that of renal cell carcinoma (RCC). Single nucleotide polymorphisms at microRNA-binding sites contribute to cancer susceptibility and progression by affecting the messenger RNA (mRNA) function of target genes. In this case-control study, we examined the frequency of six potentially functional single nucleotide polymorphisms in the LDL receptor gene (LDLR) in 1004 clear cell RCC (ccRCC) patients and 1065 cancer-free subjects. Logistic regression analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs). The association between genetic variants and levels of LDLR mRNA and protein was also evaluated. Compared with the CC genotype, multivariate logistic regression analysis showed that the LDLR rs2738464 variant GG genotype was associated with a significantly decreased ccRCC risk (P = 0.002, OR: 0.605, 95% CI: 0.439-0.833). Further functional experiments showed that the rs2738464 variant G allele affected miR-330 regulation of the LDLR 3'-untranslated region (UTR), increasing LDLR mRNA levels in patient kidney tissues. These findings suggest that LDLR rs2738464 may affect the affinity of miR-330 binding to the LDLR 3'-UTR, thus regulating LDLR expression and contributing to ccRCC risk.

Identification and validation of an eight-gene expression signature for predicting high Fuhrman grade renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a malignancy with heterogeneous outcomes. Currently, renal mass biopsies are commonly employed to extract disease characteristics and aid prognosis. Although the pathological diagnosis of malignant disease is accurate in contemporary reports, the classification of Fuhrman grade using biopsy specimens remains far from promising. To generate a gene signature to distinguish high-grade ccRCC, we used the cancer genome atlas (TCGA) database to develop a gene expression signature for distinguishing high-grade (G3/4) from low-grade (G1/2) disease. The expression profile was further validated for performance and clinical use in 283 frozen renal cancer samples and 127 ex vivo renal mass biopsy samples, respectively. The area under curve (AUC) was used to quantify discriminative ability and was compared using the De-long test. Using the discovery dataset, we identified a 24-gene signature for high-grade disease with an AUC of 0.884. After applied to the development dataset, an eight-gene profile was defined and achieved an AUC of 0.823. Accuracy of eight-gene panel was maintained in the renal mass biopsies (RMB) samples (AUC = 0.821). In summary, using three-stage design, we validated an eight-gene expression signature for predicting high Fuhrman grade of ccRCC. This tool may help to reveal the characteristics of ccRCC biopsy specimens.

ITGA2B and ITGA8 are predictive of prognosis in clear cell renal cell carcinoma patients.

Integrins play an important role in cancer growth and metastasis. This study aimed at determining the predictive ability of integrins and associated genes identified through molecular network in clear cell renal cell carcinoma. A total of 525 patients with ccRCC from The Cancer Genome Atlas (TCGA) cohorts were collected in this study. The expression profile of integrins and related genes were obtained from the TCGA RNAseq database. Clinicopathological characteristics, including age, gender, tumor size, tumor node metastasis (TNM), tumor grade, stage, laterality, and overall survival were collected. Cox proportional hazards regression model as well as Kaplan-Meier curve were used to assess the relative factors. Genes of integrin family that showed certain correlations with overall survival (OS) were further validated in the Fudan University Shanghai Cancer Center (FUSCC) cohort. In the TCGA cohort, after Cox proportional hazards analysis, ITGA2B (hazards ratio (HR) = 1.232, 95 % CI 1.097 to 1.383) and ITGA8 (HR = 0.804, 95 % CI 0.696 to 0.930) were shown predictive of ccRCC prognosis. Low ITGA8 expression was associated with poor prognosis for OS (log-rank test, p < 0.0001), while high level of ITGA2B expression was correlated with poor prognosis for OS (log-rank test, p < 0.0001). This finding was validated in FUSCC cohort (log-rank test, all p < 0.05). As a result, low ITGA8 expression was associated with poor prognosis for OS (log-rank test, p = 0.0053), while high level of ITGA2B expression was correlated with poor prognosis for OS (log-rank test, p < 0.0001). Plus, low ITGA8 expression was associated with poor prognosis for disease-free survival (DFS) in the TCGA cohort (log-rank test, p < 0.0001). In the gene cluster network analysis, GIT1 and SHC1 associated with ITGA2B and ITGA8 were identified as independent predictive factors of overall survival of ccRCC. ITGA2B, ITGA8, GIT1, and SHC1 were identified as independent prognostic factors of overall survival of ccRCC. This method may act as a tool to reveal more prognostic-associated genes in ccRCC.

ADIPOQ polymorphism rs182052 is associated with clear cell renal cell carcinoma.

Recent studies have indicated that low circulating adiponectin concentrations are associated with a higher risk of several cancers, including renal cell carcinoma. In this case-control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell renal cell carcinoma (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The association of serum adiponectin concentration with genetic variants was calculated using a multivariate linear regression model. A significantly higher ccRCC risk was associated with the rs182052 variant A allele (adjusted OR, 1.36 and 95% CI, 1.07-1.74 for AA vs GG, P = 0.013; adjusted OR, 1.27 and 95% CI, 1.04-1.56 for AA vs GG+AG, P = 0.019), and this positive association was more evident in overweight subjects. Fasting serum adiponectin was lower in subjects carrying A alleles of rs182052 in both ccRCC patients (ß = -0.399, P = 0.018) and healthy controls (ß = -0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.

Oxidized low-density lipoprotein is associated with advanced-stage prostate cancer.

Clinical and epidemiological data suggest coronary artery disease shares etiology with prostate cancer (PCa). The aim of this work was to assess the effects of several serum markers reported in cardiovascular disease on PCa. Serum markers (oxidized low-density lipoprotein [ox-LDL], apolipoprotein [apo] B100, and apoB48) in peripheral blood samples from 50 patients from Fudan University Shanghai Cancer Center (FUSCC) with localized or lymph node metastatic PCa were investigated in this study. Twenty-five samples from normal individuals were set as controls. We first conducted enzyme-linked immunosorbent assay analysis to select candidate markers that were significantly different between these patients and controls. Then, the clinical relevance between OLR1 (the ox-LDL receptor) expression and PCa was analyzed in The Cancer Genome Atlas (TCGA) cohort. We also investigated the function of ox-LDL in PCa cell lines in vitro. Phosphorylation protein chips were used to analyze cell signaling pathways in ox-LDL-treated PC-3 cells. The ox-LDL level was found to be significantly correlated with N stage of prostate cancer. OLR1 expression was correlated with lymph node metastasis in the TCGA cohort. In vitro, ox-LDL stimulated the proliferation, migration, and invasion of LNCaP and PC-3 in a dose-dependent manner. The results of phosphoprotein microarray illustrated that ox-LDL could influence multiple signaling pathways of PC-3. Activation of proliferation promoting signaling pathways (including ß-catenin, cMyc, NF-κB, STAT1, STAT3) as well as apoptosis-associating signaling pathways (including p27, caspase-3) demonstrated that ox-LDL had complicated effects on prostate cancer. Increased serum ox-LDL level and OLR1 expression may indicate advanced-stage PCa and lymph node metastasis. Moreover, ox-LDL could stimulate PCa proliferation, migration, and invasion in vitro.

Preoperative lymphocyte-monocyte and platelet-lymphocyte ratios as predictors of overall survival in patients with bladder cancer undergoing radical cystectomy.

Although pretreatment neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), and platelet-lymphocyte ratio (PLR) are reportedly associated with clinical outcomes of many cancers, their roles in patients with bladder cancer (BCa) who undergo radical cystectomy (RC) have not been widely investigated. We analyzed relationships between preoperative NLR, LMR, PLR, and overall survival (OS) in 124 BCa patients undergoing RC. OS curves were drawn using the Kaplan-Meier method and evaluated using the log-rank test. Relationships between OS and potential confounding variables were determined using Cox's proportional hazard regression model. Decreased LMR was associated with shorter OS (P = 0.012); OS in the low PLR group was significantly longer than that in the high PLR group (P = 0.029), and NLR was not significantly associated with oncological outcomes. However, after adjusting for confounding variables, patients in the high-LMR group indicated >30% decreased mortality than the low-LMR group (hazard ratio 0.674; 95% confidence interval 0.412-0.890; P = 0.003), and PLR was not an independent predictor of OS. Our results show that preoperative LMR is a better prognostic factor in BCa patients undergoing RC, compared with NLR and PLR.

Retrograde radical cystectomy and consequent peritoneal cavity reconstruction benefits localized male bladder cancer: results from a cohort study.

BACKGROUND: Bladder cancer is the second most common genitourinary malignancy. Our study was to introduce a standardized surgical procedure of retrograde radical cystectomy and consequent peritoneal cavity reconstruction in localized male bladder cancer. METHODS: Eighty-four consecutive male patients with localized bladder cancer (clinical stage T2 or lower) underwent surgery in our institute with the proposed procedure between May 2012 and April 2013. Median age was 65 years (range, 35 to 83 years); patient characteristics, surgical parameters, perioperative complications, pathology, and short-term prognosis were analyzed. Median follow-up was 24 months (range, 18 to 30 months). RESULTS: The complete procedure including urinary diversion took 4.0 h (2.2 to 5.0 h), with a median exposed peritoneal cavity of 45 min (0 to 75 min); the median blood loss was 140 ml (50 to 600 ml), and 2 patients needed transfusion; neurovascular bundles were reserved in 76 cases; the median abdominal and pelvic drainage was 9.0 days (6 to 15 days), the median gastrointestinal recovery was 2.5 days (1 to 12 days), and the median postoperative hospital stay was 13.0 days (10 to 21 days). Four patients had severe surgical complications, and two had mild to moderate ileus, with recovery in 1 and 2 weeks with supportive treatment. No perioperative deaths or postoperative recurrence were reported. CONCLUSIONS: The surgical procedure in male localized bladder cancer described in the present study provided surgical facilities, with limited abdominal organ disturbance and satisfactory tumor control. The procedure was associated with good gastrointestinal recovery, few postoperative complications, and a short hospital stay.

Is it safe to omit baseline bone scan for newly diagnosed prostate cancer patients?

OBJECTIVES: The aim of this study is to modify and validate a novel screening tool to determine the necessity of bone scans in Chinese PCa patients at the time of diagnosis. METHODS: Five-hundred-and-one patients diagnosed with PCa between 2010 and 2013 at Zhongshan Hospital, Fudan University, were included in the study. All received bone scans using technetium 99m methylene diphosphonate (99mTc-​MDP) at the initial staging. Age, prostate-specific antigen (PSA) and alkaline phosphatase (ALP) at diagnosis, disease stage, and biopsy Gleason score were collected from all patients. Multivariate logistic regression analysis and discrimination analysis were performed. A validation analysis of this screening tool was performed by Shanghai Cancer Center, Fudan University. RESULTS: Among the 501 patients, 84 (16.7%) of them had BM. The area under the ROC curve was 0.9006 (95% CI, 0.87-0.93). The sensitivity of the cut-off point was 94.1%, and the specificity was 58.3%. The validation analysis demonstrated an area under the ROC curve of 0.846 (95% CI, 0.805-0.887). CONCLUSIONS: Study results demonstrated that a baseline bone scan can be safely omitted for cT1-T3 PCa patients who have a PSA ≤39 ng/ml and an ALP ≤88 IU/l. This novel screening tool may help determine the necessity of including a bone scan at the time of initial diagnosis of PCa.

[Comparison of the renal function after partial nephrectomy and radical nephrectomy for T1a renal cell carcinoma].

OBJECTIVE: To evaluate the alterations in renal function after radical nephrectomy (RN) and partial nephrectomy (PN) for renal cell carcinoma (RCC) and to determine the risk factors for the onset of postoperative renal function impairment. METHODS: We assessed the renal function of 429 T1a RCC patients by investigating the time-dependent changes of the estimated glomerular filtration rate (eGFR) after surgery from August 2003 to August 2010. Univariate and multivariate regression models were used to determine the risk factors for the onset of an eGFR < 60 ml · min⁻¹ · 1.73 m⁻² function, and to evaluate the prognosis for the two groups. RESULTS: The mean eGFR values (ml · min⁻¹ · 1.73 m⁻²) at postoperative 1, 7 days, 1, 3, 6, 12 and 24 months were 51.4 ± 12.6, 52.1 ± 17.8, 53.2 ± 19.5, 54.6 ± 20.2, 53.8 ± 16.6, 52.7 ± 22.3 and 51.5 ± 18.4 in the RN group and 69.6 ± 18.3, 70.3 ± 19.5, 71.5 ± 21.4, 76.2 ± 22.8, 75.4 ± 19.7, 74.3 ± 16.3 and 73.1 ± 23.2 in the PN group, respectively. The eGFR of the radical nephrectomy group was significantly lower than that of the partial nephrectomy group (P < 0.05). Multivariable analysis revealed that radical nephrectomy and age were risk factors for the onset of postoperative chronic renal dysfunction. CONCLUSIONS: Renal function recovered partially after partial and radical nephrectomy and is maintained constantly after 3 months. Surgical mode and age are risk factors for the onset of postoperative eGFR < 60 ml · min⁻¹ · 1.73 m⁻² impairment. Compared with radical nephrectomy, partial nephrectomy can preserve renal function and reduce the incidence of postoperative chronic renal dysfunction.

[Influence of clinical factors on Gleason score upgrade in patients undergoing radical prostatectomy].

OBJECTIVE: To evaluate clinical factors affecting Gleason score upgrade in patients receiving radical prostatectomy (RP). METHODS: A total of 322 patients with prostate cancer who received RP from January 2012 to December 2013 at Department of Urology at Fudan University Shanghai Cancer Center were included, and their data of age, body mass index (BMI), prostate-specific antigen (PSA), prostate volume, percentage core, clinical staging, pathological characteristics, biopsy Gleason score and RP Gleason score were analyzed. Differences in categorical variables and continuous variables were compared using χ² tests and Student's t-test, respectively. Unconditional multiple logistic regression was used to estimate OR and 95% CI of the association of Gleason score upgrade with clinical factors. RESULTS: Gleason score upgrade occurred in 107 of 322 (33.3%) patients. There was no difference in age, BMI and clinical staging between the two groups. Compared with patients without Gleason score upgrade, higher levels of PSA (χ² =6.740, P=0.034), smaller prostate volume (t=3.481, P=0.002) and elevated percentage core (t=-2.097, P=0.037) were observed in patients with Gleason score upgrade. In addition, lymph node metastasis (χ² =4.193, P=0.041) and extracapsular extension (χ² =4.747, P=0.029) were more common in patients with Gleason score upgrade. After adjusting for potential confounders, PSA levels (OR=2.451, 95% CI: 1.290-4.660), prostate volume (OR=0.982, 95% CI: 0.969-0.995) and percentage core (OR=2.756, 95% CI: 1.033-7.357) were independent predictors for Gleason score upgrade. CONCLUSION: Gleason score upgrade happens at a relatively high rate. PSA levels, prostate volume and percentage core are important factors affecting Gleason score upgrade.