Efficacy of indocyanine green fluorescence-guided inguinal lymph node dissection for penile cancer: a randomised trial.

OBJECTIVES: To investigate the safety and efficacy of indocyanine green (ICG) fluorescence-guided inguinal lymph node dissection (ILND) in patients with penile cancer. PATIENTS AND METHODS: A prospective, single-blind, randomised controlled clinical trial (ChiCTR2100044584) was performed among patients with penile caner who underwent bilateral modified ILND at four centres in China between 1 April 2021 and 30 June 2022. Patients aged 18-80 years and diagnosed with squamous cell carcinomas were included. Each enrolled patient was randomly assigned to either ICG fluorescence-guided ILND by a laparoscopic or robot-assisted approach in one groin, with non-ICG fluorescence-guided ILND in the other groin acting as a control. The primary outcome was the number of retrieved ILNs. Secondary outcomes included complications according to the Clavien-Dindo classification and the ILN non-compliance (inadequate removal of ILNs) rate. RESULTS: A total of 45 patients were included in the intention-to-treat (ITT) analysis, and the 42 who completed the entire study were included in the per protocol (PP) analysis. There were no ICG-related complications in any of the patients. The results of the ITT and PP analyses indicated that the total number of unilateral ILNs retrieved was higher on the ICG side than on the non-ICG side (mean 13 vs 9 ILNs, difference 4 ILNs [95% CI 2.7-4.4], P = 0.007), and the number of unilateral deep and superficial ILNs was higher on the ICG side. Furthermore, the LN non-compliance rate was lower on the ICG side than on the non-ICG side. Additionally, there was no significant difference in local complications in the groins between the two sides (P > 0.05). CONCLUSION: An ICG fluorescence-guided ILND was safe for patients with penile cancer. This procedure can improve the number of ILNs retrieved and reduce the LN non-compliance rate without increased complications. ICG fluorescence-guided ILND is beneficial and recommended for selected patients with penile cancer.

A single-centre, open-label, single-arm, fixed-sequence pharmacokinetic study of SHR3680 on repaglinide and bupropion in prostate cancer patients.

To evaluate the pharmacokinetic effects of SHR3680 on repaglinide and bupropion and its metabolite hydroxybupropion. METHODS: A single-centre, open-label, single-arm, fixed-sequence clinical trial in 18 patients with prostate cancer. RESULTS: After a single oral dose of 0.5 mg repaglinide and SHR3680, geometric mean peak plasma concentration (Cmax ) of plasma repaglinide was 14.240 and 5.887 ng/mL, geometric mean area under the concentration-time curve (AUC0-t )was 20.577 and 7.320 h ng/mL, geometric mean AUC0-∞ was 20.949 and 7.451 h ng/mL, mean half-life (t1/2 ) was 1.629 and 1.195 hours, and geometric mean oral clearance (CL/F) was 23.867 and 67.107 L/h, respectively. After a single oral administration of 150 mg bupropion and SHR3680, geometric mean Cmax of plasma bupropion was 85.430 and 33.747 ng/mL, geometric mean AUC0-t was 1003.896 and 380.158 h ng/mL, geometric mean AUC0-∞ was 1038.054 and 401.387 h ng/mL, mean t1/2 was 22.533 and 17.733 hours, and geometric mean CL/F was 144.501 and 373.705 L/h, respectively. The plasma geometric mean Cmax of its main active metabolic hydroxybupropion was 268.113 and 177.318 ng/mL, geometric mean AUC0-t was 14 283.087 and 5420.219 h ng/mL, geometric mean AUC0-∞ was 15 218.158 and 5364.625 h ng/mL, mean t1/2 were 36.069 and 16.688 hours, and geometric mean CL/F was 8.623 L/h and 27.961 L/h, respectively. CONCLUSION: Coadministration of SHR3680 with repaglinide or bupropion significantly shortened the elimination half-lives, significantly increased the apparent clearance rate, and significantly decreased the in vivo exposure of repaglinide, bupropion and hydroxybupropion compared with single administration of repaglinide or bupropion.

Neoadjuvant Chemotherapy Benefits Survival in High-Grade Upper Tract Urothelial Carcinoma: A Propensity Score-Based Analysis.

BACKGROUND: To evaluate the benefit of neoadjuvant chemotherapy (NAC) for survival in high-grade upper tract urothelial carcinoma (UTUC), a propensity score-based analysis was performed with high-grade UTUC patients from multiple urologic centers. METHODS: From three urologic centers, 48 high-grade UTUC patients who received chemotherapy followed by surgery (NAC group) and 72 high-grade UTUC patients who underwent initial surgery (no-NAC group) were involved in a propensity score-based analysis. After propensity score-based (1:1) matching, 37 patients receiving NAC and 37 patients not receiving NAC were followed. RESULTS: The patients who received NAC had improved disease-free survival (DFS) and overall survival (OS), with a 3-year DFS rate of 78.4% and an OS rate of 86.5% versus a 3-year DFS rate of 51.4% and an OS rate of 62.2% for those treated with initial surgery (P = 0.018 and P = 0.02, respectively). In the multivariate analysis, the NAC group had a lower risk for mortality [DFS hazard ratio (HR) 0.25; 95% confidence interval (CI) 0.10-0.62; P = 0.003; OS HR 0.22; 95% CI 0.085-0.57; P = 0.002]. The analysis of patient survival in matched subgroups showed that NAC was beneficial in terms of the 3-year DFS for the group with a cT of 3 or higher (DFS HR 0.37; 95% CI 0.14-0.94; P = 0.036) and the group that had tumor with hydronephrosis (DFS HR 0.31; 95% CI 0.11-0.87; P = 0.026). CONCLUSION: The study showed that NAC may be considered as an effective addition to surgery for the treatment in high-grade UTUC patients.

Holmium laser enucleation of the prostate versus thulium laser enucleation of the prostate for the treatment of large-volume prostates > 80 ml: 18-month follow-up results.

PURPOSE: To compare the perioperative and functional outcomes of holmium laser enucleation of the prostate (HoLEP) and thulium laser enucleation of the prostate (ThuLEP) for the treatment of large-volume benign prostatic hyperplasia (BPH) (> 80 ml). METHODS: A total of 116 consecutive patients with BPH were randomized to be treated surgically with either HoLEP (n = 58) or ThuLEP (n = 58), following the classical three-lobe enucleation technique. Follow-up was assessed at 1, 3, 6, 12 and 18 months after surgery. RESULTS: At 18 months, the lower urinary tract symptom index was improved significantly in both groups compared with the baseline values. The operative time (78.4 ± 8.0 vs. 71.4 ± 6.4 min) and enucleation time (61.2 ± 5.4 vs. 56.4 ± 8.4 min) were significantly shorter for ThuLEP compared to HoLEP (both p < 0.001). There were no significant differences between the two groups regarding morcellation time, resected weight, hemoglobin decrease, catheter time and hospital stay (p > 0.05). The HoLEP and ThuLEP groups had equivalent International Prostate Symptom Scores (3 [3-3] vs. 3 [3-3], p = 0.776), quality of life (1 [1-2] vs. 2 [1-2], p = 0.809), Qmax (25.3 ± 4.8 ml/s vs. 24.7 ± 4.4 ml/s, p = 0.470), postvoid residual urine (PVR) (6.1 [2.6-20.8] vs. 7.7 [3.1-22.8] ml, p = 0.449) and PSA (0.84 ± 0.32 vs. 0.90 ± 0.34 ml, p = 0.309) at 18 months postoperatively. CONCLUSION: Both HoLEP and ThuLEP relieve lower urinary tract symptoms in a comparable way with high efficacy and safety. ThuLEP was statistically superior to HoLEP in operation time and enucleation time, although the differences were clinically negligible.

Survivin and HLA-I expression predicts survival of patients with clear cell renal cell carcinoma.

Altered expression of survivin and leukocyte antigen class I (HLA-I) proteins is associated with tumor progression. This study investigated their expressions in clear cell renal cell carcinoma (ccRCC) tissues for association with a clinical significance of ccRCC patients. Ninety ccRCC and 20 normal tissue samples (i.e., control) were immunohistochemically stained for survivin and HLA-I expression for an association with clinicopathological data and survival of ccRCC patients. Survivin protein was expressed in 82.2 % (74/90) of ccRCC tissue samples compared to 0 % in the normal tissues, and HLA-I protein was expressed in 90 % (18/20) of the normal tissues vs. 67.8 % (61/90) in ccRCC samples. Survivin expression was associated with tumor grade, stage, and lymph node metastasis (p = 0.000, p = 0.016, and p = 0.001, respectively). Conversely, lost HLA-I expression did not have any associations with clinicopathological data (p > 0.05). Survivin-negative patients had a higher tumor-free survival rate than patients with survivin expression (p = 0.037). Patients with normal HLA-I levels had a higher tumor-free survival rate than those with reduced HLA-I levels (p = 0.02). The uni- and multivariate analyses indicated that expression of survivin and HLA-I, individually and in combination, was an independent predictor for survival of ccRCC patients. Overexpression of survivin but reduced HLA-I expression is useful in the prediction of tumor-free survival of ccRCC patients.

Identification of the shared gene MXD3 signatures and biological mechanism in patients with hip pain and prostate cancer.

Prostate cancer (PRAD) is recognized as having a significant effect on systemic illnesses. This study examined possible immune cells, metabolic pathways, and genes that may explain the interaction between PRAD and hip pain. We used information retrieved from the Cancer Genome Atlas and the Gene Expression Omnibus databases. To find common genes, we utilized differential expression analysis and weighted gene co-expression network analysis. The genes that were shared were subjected to pathway enrichment studies using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Additionally, hub genes were analyzed using LASSO regression, and a receiver operating characteristic curve was generated based on the screening outcomes. The genes for the nodes were chosen in a protein-protein interaction network that was built. Single-sample gene-set enrichment analysis was performed to identify the differentially expressed genes. Immunohistochemistry staining confirmed hub gene expression, and single-sample gene-set enrichment analysis assessed immune cell infiltration. We concluded by comparing MAX dimerization protein 3 (MXD3) and MAX interactor 1 (MXI1) expression in tumor tissues using Uniform Manifold Approximation and Projection and violin plots in the Tumor lmmune Single-cell Hub database. After analyzing the intersection of the differentially expressed genes and weighted gene co-expression network analysis-significant module genes, we determined that MXD3 was the best shared diagnostic biomarker for PRAD and hip pain. One potential predictor of PRAD development was the MXI1 node gene, which was found in the protein-protein interaction network. The analyses revealed that MXD3 had a relatively positive correlation with neutrophil and T-helper cell infiltration levels, whereas MXI1 had a negative correlation with mast and Tgd cell levels. Tumors had lower levels of MXI1 expression and higher levels of MXD3 expression compared to normal tissues. Endothelial cells, induced pluripotent stem cells, and smooth muscle cells were all found to express MXI1. This is the first study to investigate the close genetic link between hip pain and PRAD using bioinformatics technologies. The 2 most significant genes involved in crosstalk between PRAD and hip pain were MXD3 and MXI1. The immunological responses triggered by T cells, mast cells, and neutrophils may be crucial in the relationship between PRAD and hip pain.

Insights into immune microenvironment and therapeutic targeting in androgen-associated prostate cancer subtypes.

Prostate cancer, one of the most prevalent malignancies among men worldwide, is intricately linked with androgen signaling, a key driver of its pathogenesis and progression. Understanding the diverse expression patterns of androgen-responsive genes holds paramount importance in unraveling the biological intricacies of this disease and prognosticating patient outcomes. In this study, utilizing consensus clustering analysis based on the expression profiles of androgen-responsive genes, prostate cancer patients from the TCGA database were stratified into two distinct subtypes, denoted as C1 and C2. Notably, the C1 subtype demonstrates a significant upregulation of certain genes, such as CGA and HSD17B12, along with a shorter progression-free survival duration, indicating a potentially unfavorable prognosis. Further analyses elucidated the immune infiltration disparities, mutation landscapes, and gene functional pathways characteristic of each subtype. Through integrated bioinformatics approaches and machine learning techniques, key genes such as BIRC5, CENPA, and MMP11 were identified as potential therapeutic targets, providing novel insights into tailored treatment strategies. Additionally, single-cell transcriptome analysis shed light on the heterogeneous expression patterns of these genes across different cell types within the tumor microenvironment. Furthermore, virtual screening identified candidate drugs targeting the BIRC5 receptor, offering promising avenues for drug development. Collectively, these findings deepen our understanding of prostate cancer biology, paving the way for personalized therapeutic interventions and advancing the quest for more effective treatments in prostate cancer management.

Oxidative Phosphorylation-Related Signature Participates in Cancer Development, and PTPRG Overexpression Suppresses the Cancer Progression in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) was a common cancer type diagnosed with frequent metastases, harboring an unfavorable therapeutic response, and results in a poor prognosis. More promising therapeutic targets are urgently required for treating ccRCC. This study was conducted to explore the role of oxidative phosphorylation in ccRCC development and reveal its clinical potential. We first identified oxidative phosphorylation-related clusters based on consensus clustering and validated their diversity in the genome instability, environmental infiltration, and immunosuppression by Gistic, ESTIMATE, GSVA, and TIDE web tools. We also compared their prognostic and clinical feature differences and predicted the IC50 level between the clusters using pRRophetic. Subsequently, we performed weighted gene coexpression network analysis to select cluster-related genes and performed functional analysis for them. The cluster-related genes were adopted to construct a risk score and nomogram for predicting patient prognosis with predictive accuracy evaluated. Finally, we performed lentivirus to induce ccRCC cell PTPRG overexpression and conducted western blot experiments to detect the critical protein expression of oxidative phosphorylation, apoptosis, cell cycle, and epithelial-mesenchymal transition processes. Also, the cell cycle and apoptosis level were evaluated by flow cytometry. As a result, we discovered that both the C1 cluster and high-risk group predicted patient survival with high accuracy and characterized lower survival rates, lower oxidative phosphorylation levels, higher immune infiltration, and malignant clinical features. Besides, we observed that overexpression of PTPRG activated oxidative phosphorylation and inhibited apoptosis. Its overexpression also depressed the epithelial-mesenchymal transition and promoted G1/S cell cycle arrest. Comprehensively, we confirmed the anticancer role of oxidative phosphorylation in ccRCC cells and discovered its association with immune and immunosuppression. PTPRG was also identified as a potential therapeutic target due to its multiple anticancer effects. We believe this study discovered a novel mechanism of ccRCC pathological progression and will provide promising targets for therapeutic strategy development.

MRI-Based Radiomics and Urine Creatinine for the Differentiation of Renal Angiomyolipoma With Minimal Fat From Renal Cell Carcinoma: A Preliminary Study.

Objectives: Standard magnetic resonance imaging (MRI) techniques are different to distinguish minimal fat angiomyolipoma (mf-AML) with minimal fat from renal cell carcinoma (RCC). Here we aimed to evaluate the diagnostic performance of MRI-based radiomics in the differentiation of fat-poor AMLs from other renal neoplasms. Methods: A total of 69 patients with solid renal tumors without macroscopic fat and with a pathologic diagnosis of RCC (n=50) or mf-AML (n=19) who underwent conventional MRI and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) were included. Clinical data including age, sex, tumor location, urine creatinine, and urea nitrogen were collected from medical records. The apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were measured from renal tumors. We used the ITK-SNAP software to manually delineate the regions of interest on T2-weighted imaging (T2WI) and IVIM-DWI from the largest cross-sectional area of the tumor. We extracted 396 radiomics features by the Analysis Kit software for each MR sequence. The hand-crafted features were selected by using the Pearson correlation analysis and least absolute shrinkage and selection operator (LASSO). Diagnostic models were built by logistic regression analysis. Receiver operating characteristic curve analysis was performed using five-fold cross-validation and the mean area under the curve (AUC) values were calculated and compared between the models to obtain the optimal model for the differentiation of mf-AML and RCC. Decision curve analysis (DCA) was used to evaluate the clinical utility of the models. Results: Clinical model based on urine creatinine achieved an AUC of 0.802 (95%CI: 0.761-0.843). IVIM-based model based on f value achieved an AUC of 0.692 (95%CI: 0.627-0.757). T2WI-radiomics model achieved an AUC of 0.883 (95%CI: 0.852-0.914). IVIM-radiomics model achieved an AUC of 0.874 (95%CI: 0.841-0.907). Combined radiomics model achieved an AUC of 0.919 (95%CI: 0.894-0.944). Clinical-radiomics model yielded the best performance, with an AUC of 0.931 (95%CI: 0.907-0.955). The calibration curve and DCA confirmed that the clinical-radiomics model had a good consistency and clinical usefulness. Conclusion: The clinical-radiomics model may be served as a noninvasive diagnostic tool to differentiate mf-AML with RCC, which might facilitate the clinical decision-making process.

Clinical Effect of Retroperitoneal Laparoscopic Radical Nephrectomy on Renal Cell Carcinoma, the Influence of Renal Function, and the Influencing Factors of Recurrence.

Renal cell carcinoma is abbreviated as renal carcinoma, and its clinical symptoms are basically hematuria, lumbago, and abdomen bump. As people's lifestyles change, the incidence of renal carcinoma continues to rise due to factors such as smoking and obesity. At present, surgical treatment is mostly used in clinical practice. Traditional open radical nephrectomy (ORN) is one of the main methods for clinical treatment of renal carcinoma. However, due to its large wound and large amount of intraoperative blood loss, the renal function of patients after surgery is poor, which is not conducive to the postoperative recovery of patients. Retroperitoneal laparoscopic radical nephrectomy (RLRN) has been widely used in the surgical treatment of renal cancer due to its advantages of small wound, less bleeding, and rapid recovery. The purpose of this study was to investigate the efficacy of RLRN in the treatment of renal cancer patients and its effect on renal function and to analyze the related factors affecting postoperative recurrence of patients. We adopt ORN and RLRN, two kinds of treatment, in patients with renal cancer surgery way, contrast analysis of the two groups of operation time, intraoperative blood loss, postoperative intestinal function recovery time, drainage tube indwelling time, length of hospital stay, and other clinical indicators and renal function indexes and use the single factor analysis and multifactor analysis, the relevant factors that affect kidney cancer patients with postoperative recurrence. The results showed that, compared with ORN treatment, RLRN treatment of renal cancer patients has a short operation time, less trauma, quick recovery after surgery, and fewer complications and can effectively alleviate the renal function injury and the body's inflammatory response, which is worthy of promotion. Postoperative recurrence was related to age, tumor diameter, TNM stage, surgical method, and postoperative immunotherapy.

Comprehensive Characterization of Ageing-Relevant Subtypes Associated With Different Tumorigenesis and Tumor Microenvironment in Prostate Cancer.

Objective: Accumulated evidence demonstrates that ageing is a robust risk factor of prostate cancer prognosis. Herein, we conducted a systematic analysis about ageing-relevant molecules and relevant tumor microenvironment features in prostate cancer. Methods: Transcriptome data, clinical information, and mutational data of prostate cancer patients were retrospectively collected from the Cancer Genome Atlas cohort. In accordance with the expression of specific ageing-relevant genes, prostate cancer patients were clustered with consensus clustering analyses. WGCNA was adopted for determination of subtype-associated co-expression modules and genes. Thereafter, characteristic genes were further screened with random forest algorithm and a prognostic model was conducted with multivariate cox regression analyses. Tumor microenvironment-infiltrating immune cells were estimated with ssGSEA and ESTIMATE. Activities of the cancer immunity cycle and expressions of HLA and immune checkpoint molecules were then quantified across prostate cancer cases. A serious experiment was conducted to investigate the roles of EIF2S2 in prostate tumorigenesis. Results: This study characterized three ageing-relevant subtypes (C1, C2, and C3) with diverse clinical prognosis. Subtype C1 presented the features of low mutational frequency and immune activation; C2 was characterized by stromal and immune activation; and C3 showed immune suppression. An ageing-derived gene signature was conducted, which independently and robustly predicted patients' prognosis. Additionally, this signature was in relation to immune inactivation. Among the genes in the signature, EIF2S2 triggered proliferation, invasion, and migration of LNCaP and PC-3 cells. Conclusion: Collectively, ageing-relevant molecular subtypes and gene signature might be of great significance to determine clinical outcomes and tumor microenvironment features and immunotherapeutic responses in prostate cancer.

The lncRNA Signatures of Genome Instability to Predict Survival in Patients with Renal Cancer.

Long noncoding RNAs (lncRNAs) exert an increasingly important effect on genome instability and the prognosis of cancer patients. The present research established a computational framework originating from the mutation assumption combining lncRNA expression profile and somatic mutation profile in the genome of renal cancer to assess the effect of lncRNAs on the gene instability of renal cancer. A total of 45 differentially expressed lncRNAs were evaluated to be genome-instability-associated from the high and low cumulative somatic mutations groups. Then we established a prognosis model based on three genome-instability-associated lncRNAs (AC156455.1, AC016405.3, and LINC01234)-GlncScore. The GlncScore was then verified in testing cohort and the total TCGA renal cancer cohort. The GlncScore was evaluated to have an accurate prediction for the survival of patients. Furthermore, GlncScore was associated with somatic mutation patterns, indicating its capacity of reflecting genome instability in renal cancer. In conclusion, this study evaluated the effect of lncRNAs on genome instability of renal cancer and provided new hidden cancer biomarkers related to genome instability in renal cancer.

Correlation Between the Evolution of Somatic Alterations During Lymphatic Metastasis and Clinical Outcome in Penile Squamous Cell Carcinoma.

Penile squamous cell carcinoma (PSCC) is a rare malignancy with poor survival after standard treatment. Although genomic alterations of PSCC have been characterized in several latest studies, the association between the formation of somatic landscape and regional lymph node metastasis (LNM), an important predictor for patient survival, has not been comprehensively investigated. Here, we collected formalin-fixed paraffin-embedded tumor tissue and matched normal samples of 32 PSCC patients, including 14 LNM patients and 18 clinically node-negative patients, to implement a whole-exome sequencing. Comparison of genomic features among different lymph node status subgroups was conducted after genomic profiling and its effects on patient survival were explored. Top-ranked recurrent gene mutants in our PSCC cohort were TP53 (13/32), NOTCH1 (12/32), CDKN2A (11/32), TTN (9/32) and FAT1 (8/32), mainly identified in the Notch, Hippo, cell cycle, TP53, RTK-RAS and PI3K pathways. While CDKN2A was confirmed to be the driver gene in all PSCC patients, certain gene mutants were significantly enriched in LNM involved patients, including TP53 (9/14 vs. 4/18, p = 0.029) and GBF1 (4/14 vs. 0/18, p = 0.028). Overall survival stratification of PSCC patients were found to be significantly correlated with mutations of three genes, including PIK3CA (Hazard ratio [HR] = 4.15, p = 0.029), CHD7 (HR = 4.82, p = 0.032) and LAMC3 (HR = 15.9, p < 0.001). PIK3CA and LAMC3 held a higher prevalence in patients with LNM compared to those without LNM (PIK3CA: 3/14 vs. 1/18, LAMC3: 2/14 vs. 1/18). Our finding demonstrated that genomic divergence exists across PSCC patients with different lymph node statuses, and it may be correlated with their survival outcome. It helps delineate somatic evolution during tumor progression and perfect potential therapeutic intervention in this disease.

SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer.

BACKGROUND: Almost all metastatic hormone-sensitive prostate cancers (mHSPC) will develop into metastatic castration-resistant prostate cancer (mCRPC) after androgen deprivation therapy (ADT). The expression level of squalene monooxygenase (SQLE) is increased in CRPC cells and regulates cholesterol metabolism. This study verified the biological function and mechanisms of SQLE in CRPC. METHODS: The expression of SQLE in human prostate cancer cells was overexpressed or silenced and its efficacy on cell survival was determined by the MTS test. Energy metabolism phenotype test was evaluated by XF real-time ATP rate assay, XF cell mitochondrial stress test, XF glycolysis stress test and XF mito fuel flex test. Cell migration and invasion were evaluated by colony formation assays and transwell assays; the expression of mRNA and protein was assessed by RT-qPCR and Western blot, respectively. Moreover, BALB/c nude mice model was performed to evaluate the lymph node metastasis. RESULTS: In our study, we found that the expression level of SQLE was significantly increased in bicalutamide-resistant-C4-2B cells compared to LNCaP cells. SQLE knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and reduced lymph node metastasis by inhibiting fatty acid oxidation in mitochondria. We also found that terbinafine, the specific inhibitor of SQLE, can enhance the sensitivity of prostate cancer cells to bicalutamide. CONCLUSION: Our study revealed that SQLE is involved in the progression of castration resistance in CRPC through mediating metabolic reprogramming, presenting SQLE as a new target for the treatment of mCRPC.

Clinical Characterization of Mismatch Repair Gene-Deficient Metastatic Castration-Resistant Prostate Cancer.

Mismatch repair-deficient (dMMR) prostate cancer is rare and has not been well studied. We aimed to evaluate the clinical characterization of dMMR metastatic castration-resistant prostate cancer (mCRPC) patients. The MMR genes include MLH1, MLH3, MSH2, MSH6, PMS1, PMS2, and EPCAM, and were analyzed by targeted sequencing of plasma cell-free DNA samples. A total of 109 mCRPC patients were identified, including 50 patients with MMR alterations (pathogenic alterations, n = 7; alterations of unknown significance, n = 43) and 59 patients with wild-type MMR. For the seven patients with pathogenic MMR alterations, the median age at diagnosis was 63.5 years, and 42.9% had a Gleason score ≥8. The median time from androgen deprivation therapy (ADT) initiation to CRPC was 24 months. Compared with the wild-type MMR subgroup, patients with MMR alterations, pathogenic MMR alterations, or MMR alterations of unknown significance showed higher rates of hotspot missense mutations or copy number amplifications in the AR gene (24/50 vs. 10/59, P = 7.8 × 10-4; 7/7 vs. 10/59, P = 2.5 × 10-5; 17/43 vs. 10/59, P = 0.013). The presence of any MMR alterations was associated with an inferior response to abiraterone [median progression-free survival (PFS): 5.0 vs. 10.9 months, P = 0.022]. Shorter PFS times were observed in both the pathogenic MMR alteration subgroup (median PFS: 5 months) and the MMR alterations of unknown significance subgroup (median PFS: 5.3 months), compared with the PFS of those with wild-type MMR genes (median PFS: 10.9 months, P = 0.052). There was no statistically significant difference in response to docetaxel chemotherapy between the MMR alterations of unknown significance and the wild-type MMR subgroups (median PFS: 8.2 vs. 8.1 months, P = 0.23). Our results demonstrate that dMMR mCRPC patients have an equivalent response to standard ADT and taxane-based chemotherapy treatments compared with wild-type MMR patients. Patients with both pathogenic and unknown significance alterations of MMR genes had poorer responses to abiraterone therapy.

Long noncoding RNA DNM3OS promotes prostate stromal cells transformation via the miR-29a/29b/COL3A1 and miR-361/TGFß1 axes.

Transforming growth factor-ß1 (TGFß1)-induced differentiation into and the activation of myofibroblasts have been regarded as critical events in benign prostatic hyperplasia (BPH); however, the underlying mechanisms of BPH pathogenesis remain unclear. Microarray profiling, STRING analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and Gene Ontology (GO) enrichment analysis were performed to confirm the candidate genes and long non-coding RNA (lncRNAs) related to BPH. Collagen Type III (COL3A1) was significantly upregulated by TGFß1 in prostate stromal cells (PrSCs) and might be involved in DNM3OS function in myofibroblasts upon TGFß1 stimulation. Upon TGFß1 stimulation, COL3A1 protein was decreased by DNM3OS silencing. miR-29a and miR-29b could directly bind to the DNM3OS and COL3A1 3' untranslated region (UTR)s to negatively regulate their expression, and by serving as a competing endogenous RNAs (ceRNA), DNM3OS competed with COL3A1 for miR-29a/29b binding, therefore counteracting miR-29a/29b-mediated COL3A1 suppression. The effect of DNM3OS silencing on ECM components and TGFß1 downstream signaling was similar to that of the TGFß1 inhibitor SB431542. miR-361 could target DNM3OS and TGFß1; DNM3OS competed for miR-361 binding to counteract miR-361-mediated TGFß1 suppression. In conclusion, we identified DNM3OS as a specifically-upregulated lncRNA upon TGFß1 stimulation in PrSCs; by serving as a ceRNA for the miR-29a/29b cluster and miR-361, DNM3OS eliminated miRNA-mediated suppression of COL3A1 and TGFß1, thereby promoting TGFß1-induced PrSC transformation into myofibroblasts.

Promoter DNA methylation analysis reveals a combined diagnosis of CpG-based biomarker for prostate cancer.

BACKGROUND: Prostate cancer (PCa) is the most common tumor in elderly men. However, the specificity and sensitivity of serum prostate-specific antigen levels in PCa diagnosis are controversial. This study aims to reveal a novel diagnosis biomarker in PCa. MATERIALS AND METHODS: The differential methylated CpG sites between 423 primary PCa and 39 adjacent samples from The Cancer Genome Atlas (TCGA) on Illumina HumanMethylation 450 platform were analyzed. The diagnostic methylation markers were mined using the Prediction Analysis of Microarrays package in Bioconductor. Then, the Gene Expression Omnibus data was used for verification. Pyrosequencing was applied to improve methylation levels of five CpGs (cg06363129, cg08843517, cg05385513, cg07220448 and cg11417025). RESULTS: The area under curve of receiver operating characteristic of eight diagnostic methylation CpGs (cg06363129, cg08843517, cg03576469, cg05385513, cg07220448, cg11417025, cg20883831, and cg23824801) in TCGA data ranged from 0.910 to 0.939. Except for cg20883831 and cg23824801, the correlations between methylation levels of six other sites and their expressions in patients were significant (r > 0.5 and P < 0.001). The methylation level of cg06363129 was significantly different between the groups of Gleason Score (GS) = 7 and GS ≥ 8 (P < 0.05). Pyrosequencing in our samples confirmed that four diagnostic methylation sites (cg06363129, cg08843517, cg05385513, and cg11417025) had high diagnostic efficacy. CONCLUSIONS: The combined diagnosis of four methylation CpGs sites (cg06363129, cg08843517, cg05385513, and cg11417025) in the gene promoter has high tissue specificity and diagnostic efficacy for PCa. Results revealed a novel potential biomarker for prostate cancer diagnosis.

Recurrent waist tumor subsequent to percutaneous nephrolithotomy: A case report.

The present study reports the case of a 39-year old male patient with a recurrent waist tumor that occurred subsequent to percutaneous nephrolithotomy (PCNL). The patient initially underwent PCNL for the management of right calculus of the kidney. Six years later, the patient underwent local mass resection for a tumor at the waist, which was subsequently diagnosed as adenocarcinoma. However, seven months subsequent to local resection, the patient presented to the Affiliated Cancer Hospital of Xiangya Medical School with a one-month history of a recurrent tumor located at the right waist. Physical examination identified no visible skin lesions; however, a palpable hard nodule was present over the right waist. Imaging studies, consisting of computed tomography (CT) and positron emission tomography-CT, indicated no additional metastases. Therefore, the patient underwent local mass resection of the waist tumor. Subsequent histological examination determined a diagnosis of metastatic adenocarcinoma. Considering the previously conducted PCNL surgery and the diagnosis, it is proposed that the recurrent waist tumor originated from renal cell carcinoma (RCC), also termed renal adenocarcinoma. However, no evidence of the original RCC tumor was identified. Therefore, the selection of an effective treatment strategy was challenging.

Malignant priapism secondary to isolated penile metastasis from a renal pelvic carcinoma.

We report a case of isolated penile metastasis from renal pelvic carcinoma in a 69-year-old man with malignant priapism. The patient had radical resection of the renal pelvic carcinoma 2 months earlier with urothelial carcinoma (UC) and sarcomatoid differentiation histology. Physical examination showed no visible skin lesions, but a palpable hard nodule was present over the penile shaft. The imaging studies did not reveal other metastases. Cavernous-Glans shunt and nodule resection were performed, and histological examination showed metastasis UC with sarcomatoid differentiation. To our knowledge, we describe the first case of malignant priapism due to isolated penile metastasis of renal pelvic carcinoma.