Peripheral Coagulation Parameters and Prostate Cancer Association: A Retrospective Study and Mendelian Randomization.

Background: The limitations of prostate-specific antigen (PSA) in diagnosing prostate cancer (PCa) necessitate the exploration of novel biomarkers. Recent studies suggest a potential link between coagulation markers, particularly fibrinogen and D-dimer, and PCa. Methods: A retrospective single-center analysis on 466 biopsy-undergone patients was conducted, categorized into PCa and benign prostatic hyperplasia (BPH) groups. Baseline and coagulation parameter levels were analyzed. Utilizing a Mendelian randomization (MR) approach, we investigated the causative relationship between D-dimer and PCa risk. Results: Individuals with PCa, compared with those with BPH, exhibited significantly higher D-dimer levels (P < .001), total PSA (P < .001), and PSA density (P < .001). Fibrinogen levels did not exhibit significant differences (P = .505). The MR analysis suggested a probable causal link between elevated D-dimer levels and an increased risk of PCa (odds ratio: 1.81, 95% confidence interval: 1.48-2.21, P = 7.4 × 10-9). Conclusions: This research highlights D-dimer as a potential biomarker for diagnosing PCa, supported by clinical and MR analyses. The study paves the way for future large-scale, multi-center research to corroborate these findings and further explore the relationship between coagulation markers and PCa mechanisms.

Development of a Nomogram Model to Identify Appropriate Candidates from Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma Based on the Surveillance, Epidemiology and End Results Database.

BACKGROUND: Although a survival benefit was observed in patients with metastatic renal cell carcinoma (mRCC) who underwent cytoreductive nephrectomy (CN), there is a lack of effective tools for predicting which individuals are likely to benefit from surgical intervention. Herein, we developed a predictive model using data from the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Patients diagnosed with mRCC were screened from the SEER database (2010-2020), supplemented by patients from East Asia. Patients were categorized into surgical and non-surgical groups, with propensity score matching conducted to balance baseline characteristics. Logistic regression analysis was performed to identify independent factors associated with benefits and a nomogram was constructed based on these factors. RESULTS: This study included 11,044 cases from the SEER database and 50 cases from an external validation cohort. CN was identified as an independent protective factor for OS. A nomogram was established, and it performed well in the training and validation sets. The calibration curves and DCA confirmed that the nomogram model could precisely predict the probability of surgical benefit. We used the nomogram to classify surgical patients into benefit and non-benefit groups. Then, we found that OS was significantly higher in the benefit group than in the non-benefit group. The external validation cohort observed the same result (P=0.035). CONCLUSION: While CN offers potential benefits for patients with mRCC, its applicability varies across the patient population. Our study constructed a nomogram that quantitatively assesses the likelihood of surgical benefit in mRCC patients, facilitating more tailored therapeutic decision-making.

Construction and evaluation of a novel prognostic risk model of aging-related genes in bladder cancer.

Background: Bladder cancer (BLCA) is the most common malignancy of the urinary system. Muscle-invasive bladder cancer (MIBC), which constitutes approximately 25% of all BLCA cases, is characterized by frequent recurrence and early onset of metastasis. Bladder cancer most commonly occurs in elderly patients and is significantly associated with aging. However, the prognostic value of age-related genes in BLCA, especially in MIBC, remains unclear. Materials and methods: Training and testing sets were obtained from The Cancer Genome Atlas BLCA project. Differentially expressed genes between BLCA and normal samples intersected with human aging-related genes. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to identify prognostic aging-related signatures, followed by the construction of a risk score model and nomogram. Kaplan-Meier and receiver operating characteristic analyses were conducted to assess the predictive power. An independent BLCA cohort of 165 samples was included for external validation. The CIBERSORT algorithm was used to explore the characteristics of the immune microenvironment. Results: Seven genes (IGF1, NGF, GCLM, PYCR1, EFEMP1, APOC3, and IFNB1) were identified by Cox and least absolute shrinkage and selection operator analyses. After combining the gene signature with the clinical parameters of patients with BLCA, a risk-prognosis model and nomogram were constructed and validated with the testing set. Bladder cancer cases with high 7-gene signature scores (high-risk group) and low scores (low-risk group) showed distinct prognoses. Furthermore, 7 types of immune cells were significantly altered between the low- and high-risk groups. Conclusions: Collectively, our data provide a 7-gene signature that serves as a potential biomarker for BLCA, especially MIBC. Moreover, this 7-gene signature highlights the role of the tumor immune microenvironment in prognosis and thus might be related to the response to anti-programmed cell death protein 1-based immunotherapy.

Integrative exploration of the mutual gene signatures and immune microenvironment between benign prostate hyperplasia and castration-resistant prostate cancer.

BACKGROUND: Benign prostate hyperplasia (BPH) and prostate cancer (CaP) are among the most frequently occurring prostatic diseases. When CaP progressed to castration-resistant CaP (CRPC), the prognosis is poor. Although CaP/CRPC and BPH frequently coexist in prostate, the inter-relational mechanism between them is largely unknown. METHODS: Single-cell RNA sequencing, bulk-RNA sequencing, and microarray data of BPH, CaP in the Gene Expression Omnibus database were obtained and comprehensively analyzed. Weighted Gene Co-Expression Network Analysis (WGCNA) and lasso regression analysis were performed to explore the potential biomarkers. RESULTS: With WGCNA, five modules in BPH, two in CaP, and three in CRPC were identified as significant modules. Pathway enrichment analysis found that the epigenetics and chromosomal-related signaling were dominantly clustered in the CaP group but not in BPH and CRPC. Lasso regression analysis was used to analyze further the mutual genes between the BPH module and the CRPC module. As a result, DDA1, ERG28, OGFOD1, and OXA1L were significantly correlated with the transcriptomic features in both BPH and CRPC. More importantly, the role of the four gene signatures was validated in two independent anti-PD-1 immunotherapy cohort. CONCLUSION: This study revealed the shared gene signatures and immune microenvironment between BPH and CRPC. The identified hub genes, including DDA1, ERG28, OGFOD1, and OXA1L, might be potential therapeutic targets for facilitating immunotherapy in prostate cancer.

Case report: Sarcomatoid urothelial carcinoma of the renal pelvis masquerading as a renal abscess.

Sarcomatoid urothelial carcinoma (SUC), a rare tumor of the urinary tract epithelium, exhibits a high degree of malignancy and therefore a poor prognosis. Due to the absence of specific clinical presentations and imaging findings, SUC of the renal pelvis masquerades as a renal abscess is frequently under-recognized or misdiagnosed as benign inflammatory disease, resulting in delayed or erroneous treatment. Here, we report a patient with SUC of the renal pelvis who presented with a renal abscess. Repeated anti-inflammatory treatment was ineffective. Unexpectedly, cancerous cells were detected in subsequent exfoliative cytology of nephrostomy drainage fluid. In accordance with this, radical surgery and postoperative chemotherapy were conducted. Fortunately, neither recurrence nor metastasis occurred during a one-year follow-up.

Ductal adenocarcinoma of the prostate or seminal vesicle adenocarcinoma: An multi-disciplinary team (MDT) case report and literature review.

We introduced a 61-year-old male with ductal adenocarcinoma of the prostate who underwent a tortuous diagnosis and treatment. Multi-disciplinary team meetings organized by our hospital have shown great value in the whole process. The patient presented with gross hematuria accompanied by frequent urination initially, and was diagnosed with ductal adenocarcinoma of the prostate involving right seminal vesicle gland and urethra by urethroscopy biopsy. The clinical stage of tumor was T3bN0M0. After 4 cycles of neoadjuvant chemotherapy, the tumor shrank significantly and the patient underwent a laparoscopic radical prostatectomy. But the patient declined to continue chemotherapy postoperatively. After 10 months, the serum prostatic specific antigen increased to 0.05 ng/mL, and multiple metastases were found in the patient's bilateral lungs. However, an unexpected diagnosis of seminal vesicle adenocarcinoma was put forward from another hospital after supplementary pathologic immunohistochemical examination. Then, after careful discussion and demonstration by our multi-disciplinary team experts, we insisted on the diagnosis of ductal adenocarcinoma of the prostate and suggested that the original regimen of chemotherapy should be continued. Up-to-date, 14 months after the operation, the patient continues to survive while undergoing ongoing active treatment as recommended.

Primary spindle cell sarcoma of the seminal vesicle: A case report and literature review.

We report a case of primary seminal vesicle spindle cell sarcoma of a 57-year-old man who underwent multiple surgical treatment. The first diagnosis of a local hospital was a right seminal vesicle cyst, so only laparoscopic decompression was performed. Postoperatively, the patient gradually developed lower abdominal discomfort, frequent and urgent urination, dysuria and constipation. Digital rectal examination palpated a heterogeneous mass. Magnetic resonance imaging showed a multilocular cystic mass of about 4.5 cm in diameter in the right seminal vesicle, which was diagnosed as a recurrent cyst. The patient underwent a second operation in our hospital, but the tumour could not be completely removed because of severe peripheral adhesions. The postoperative pathological diagnosis was seminal vesicle cystadenoma with spindle cell sarcoma. One month later, a computed tomography scan performed at another hospital showed that the mass had invaded the bladder and sigmoid colon. The pathological diagnosis of re-examination was spindle cell liposarcoma. After neoadjuvant chemotherapy, extended resection of the tumour was performed, and adjuvant chemotherapy was continued after surgery. The total duration of follow-up was 19 months and 3 months after the third surgery. The patient survived with no recurrence or metastasis.

Clinical evaluation of tamsulosin in the relief of lower urinary tract symptoms in advanced prostate cancer patients.

PURPOSE: To assess the effectiveness and safety of tamsulosin combined with androgen deprivation therapy (ADT) for lower urinary tract symptoms (LUTS) in advanced prostate cancer (PC) patients. METHODS: Ninety PC patients with moderate-to-severe LUTS randomized into two groups of 45 each. One group received ADT (group 1), and the other received ADT plus tamsulosin (group 2) for 24 weeks. The outcome measures were changes in the International Prostate Symptom Score (IPSS), IPSS obstructive and irritative subscores, quality of life (QoL), maximum urinary flow rate (Q max), post-voiding residual (PVR) and prostate-specific antigen (PSA) from baseline. The treatment response was monitored at 8, 16 and 24 weeks. RESULTS: Both ADT monotherapy and ADT plus tamsulosin significantly improved IPSS,QoL score, Q max and PVR at the end of the treatment period. ADT plus tamsulosin had a greater impact on total IPSS, IPSS obstructive subscore, QoL and PVR at week 8 and week 16 than ADT monotherapy. Tamsulosin group showed greater improvement in Q max than ADT group. Significant improvements of IPSS, IPSS obstructive subscore and QoL were achieved at early treatment stage (week 8) in group 2, whereas similar improvements were achieved at week 16 in group 1. There were no significant differences in IPSS, IPSS subscores, QoL and PVR between the two groups at week 24. CONCLUSIONS: Additional administration of tamsulosin showed significantly greater and sooner relief in LUTS than ADT monotherapy, with good acceptability. It is feasible that ADT is used alone after 16-24 weeks of combination therapy.

Elevated expression of HIF-lα in actively growing prostate tissues is associated with clinical features of benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is one of the most common diseases in middle-age or older men. Increasing evidence has shown that BPH is associated with hypoxia microenvironment. METHODS: We retrospectively collected patient data and tissue samples from fetal prostates(FP), normal prostates(NP), intra-acinar of BPH, peri-acinar of BPH, prostate cancers and sarcomas of prostate. The expression of HIF-1α, as well as VEGF was visualized by immunohistochemistry and statistically analyzed with clinical parameters. RESULTS: Expression of HIF-lα was observed in intra-acinar of BPH (69.5%), prostate cancer (85.7%) and all FPs, while NP and peri-acinar of BPH tissues were all stained negative. HIF-lα levels in FPs and the malignant tumors were higher than BPH tissues(p < 0.05), and the expression of HIF-lα in intra-acinar of BPH was higher than NP and peri-acinar of BPH (p < 0.05). The expression of HIF-lα was correlated with the weight of intra-acinar of prostate (p < 0.05). And patients with prostate weight larger that 72.45g were prone to have HIF-lα moderate-positive expression, according to the ROC curve (AUC = 0.734, 95%CI = 0.630-0.838). Moreover, the risk of acute urine retention (AUR) for HIF-lα moderate-positive patients increased significantly (OR=5.517, 95%CI = 2.434-12.504). CONCLUSIONS: HIF-lα expression is increased in highly proliferative prostate tissues and correlated with the weight of intra-acinar prostate. Moreover, HIF-lα is also an independent risk factor for AUR occurrence in BPH patients.

Treatment of Renal Stones ≥20 mm with Extracorporeal Shock Wave Lithotripsy.

AIMS: To identify subgroups of patients with renal stones ≥20 mm that are more suitable for extracorporeal shock wave lithotripsy (ESWL) monotherapy. METHODS: A total of 376 patients with renal stones ≥20 mm underwent monotherapy with ESWL. The treatment outcome was evaluated after 3 months of follow-up. A stone-free status or fragmentation of stones to 4 mm or smaller was considered efficacious. RESULTS: At 3 months after treatment, the overall stone-free rate was 64.4%, and the efficacy rate was 70.7%. The efficacy rate was 89.4% for patients with a residual stone surface area ≤50% of baseline after the first ESWL, while the efficacy rate was 32.4% for other patients. The efficacy was 92.2% for stones ≤400 mm2 and those with lower radiodensity, as determined by a plain (KUB) film. CONCLUSIONS: For renal stones with a surface area ≤400 mm2 and a radiodensity equal to or less than that of the 12th rib as determined by a KUB film, ESWL may be considered the first line of treatment, even for stones with a diameter ≥20 mm. For large stones requiring repeat treatments, the surface area of the residual stones after the first ESWL is a predictor of the final treatment result.

Eg5 inhibitor, a novel potent targeted therapy, induces cell apoptosis in renal cell carcinoma.

Eg5 is critical for mitosis and overexpressed in various malignant tumors, which has now been identified as a promising target in cancer therapy. However, the anti-cancer activity of Eg5 inhibitor in renal cell carcinoma (RCC) remains an open issue. In this paper, we evaluated, for the first time, the therapeutic benefit of blocking Eg5 by S-(methoxytrityl)-L-cysteine (S(MeO)TLC) in RCC both in vitro and vivo. The expression of Eg5 was examined in clinical tissue samples and various kidney cell lines, including 293T, 786-0, and OS-RC-2. The anti-proliferative activity of Eg5 inhibitors, (S)-trityl-L-cysteine (STLC) and S(MeO)TLC, was evaluated by a cell viability assay. An apoptosis assay with Hoechst nuclear staining and flow cytometry was applied to investigate the efficacy of the S(MeO)TLC, which is more potent than STLC. Immunofluorescence was used to research the possible mechanism. Furthermore, in vivo studies were performed by using subcutaneous xenograft models, which were used to confirm its role as a potential anti-neoplastic drug. The Eg5 expression was detected in kidney cell lines and RCC tissues, which was low in normal kidney samples. STLC and S(MeO)TLC exhibited their optimal anti-proliferative activity in 72 h, and cells treated with S(MeO)TLC presented characteristic monoastral spindle phenotype in 24 h and apoptotic cells in 48 h. In vivo, S(MeO)TLC effectively suppressed tumor growth in subcutaneous xenograft models. Inhibition of Eg5 represses the proliferation of RCC in vitro and in vivo. All these findings collectively demonstrate that S(MeO)TLC, a potent Eg5 inhibitor, is a promising anti-cancer agent for the treatment of RCC.

High mobility group box 1 protein is methylated and transported to cytoplasm in clear cell renal cell carcinoma.

BACKGROUND: The high mobility group box 1 (HMGB1) protein is a widespread nuclear protein present in most cell types. It typically locates in the nucleus and functions as a nuclear cofactor in transcription regulation. However, HMGB1 can also localize in the cytoplasm and be released into extracellular matrix, where it plays critical roles in carcinogenesis and inflammation. However, it remains elusive whether HMGB1 is relocated to cytoplasm in clear cell renal cell carcinoma (ccRCC). METHODS: Nuclear and cytoplasmic proteins were extracted by different protocols from 20 ccRCC samples and corresponding adjacent renal tissues. Western blotting and immunohistochemistry were used to identify the expression of HMGB1 in ccRCC. To elucidate the potential mechanism of HMGB1 cytoplasmic translocation, HMGB1 proteins were enriched by immunoprecipitation and analyzed by mass spectrometry (MS). RESULTS: The HMGB1 protein was overexpressed and partially localized in cytoplasm in ccRCC samples (12/20, 60%, p<0.05). Immunohistochemistry results indicated that ccRCC of high nuclear grade possess more HMGB1 relocation than those with low grade (p<0.05). Methylation of HMGB1 at lysine 112 in ccRCC was detected by MS. Bioinformatics analysis showed that post-translational modification might affect the binding ability to DNA and mediate its translocation. CONCLUSION: Relocation of HMGB1 to cytoplasm was confirmed in ccRCC. Methylation of HMGB1 at lysine 112 might the redistribution of this cofactor protein.