{"title":"Neoadjuvant chemohormonal therapy before radical prostatectomy in high-risk prostate cancer: a mini-review.","authors":"Junjie Fan, Zhangdong Jiang, Guojing Wang, Dalin He, Kaijie Wu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>High-risk localized prostate cancer (PCa) has the potential of recurrence and progression to a lethal phenotype, and neoadjuvant therapy followed by radical prostatectomy (RP) may be an option for these patients. Docetaxel has been recently shown to be an effective chemotherapeutic agent for high-volume metastatic hormone-sensitive PCa and metastatic castration-resistant PCa, and these increased efficacy create the impetus to assess the potential role of preoperative docetaxel in high-risk localized PCa. In this mini-review, we found that neoadjuvant chemohormonal therapy (NCHT) may be an effective neoadjuvant regimen to improve oncological outcome of high-risk PCa. However, the addition of docetaxel in the neoadjuvant setting would unavoidably increase the rate of adverse events, impose additional economic burdens. Therefore, suitable patient selection is crucial and pathological response might be a surrogate endpoint. Furthermore, we also found that molecular imaging prostate-specific membrane antigen (PSMA) PET/CT was a promising tool to evaluation the effectiveness of NCHT, and the expression status of AR, AR-V7, Ki-67, PTEN and TP53 might be helpful for urologists to identify more suitable candidates for NCHT.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"12 1","pages":"1-7"},"PeriodicalIF":1.2,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kyra Gassmann, Kavita Gupta, Raymond Khargi, Anna Ricapito, Alan J Yaghoubian, William M Atallah, Blair Gallante, Mantu Gupta
{"title":"Review of efficacy and safety of same-day discharge after percutaneous nephrolithotomy.","authors":"Kyra Gassmann, Kavita Gupta, Raymond Khargi, Anna Ricapito, Alan J Yaghoubian, William M Atallah, Blair Gallante, Mantu Gupta","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Prior literature reviews have assessed the efficacy and safety of outpatient percutaneous nephrolithotomy (PCNL) with \"outpatient\" defined as discharge within twenty-four hours of surgery. To our knowledge, this is the first literature review analyzing ambulatory PCNLs (aPCNL) defined as hospital discharge on the same day as surgery. This review aims to assess the efficacy and safety of same-day discharge after PCNL.</p><p><strong>Methods: </strong>We conducted a search in the PubMed database for key search terms including \"ambulatory PCNL\", \"ambulatory percutaneous nephrolithotomy\", \"outpatient PCNL\", \"outpatient percutaneous nephrolithotomy\", and \"day surgery percutaneous nephrolithotomy\". We reviewed articles defining \"ambulatory\" as discharge the same day the PCNL was performed. 13 papers were identified in our search.</p><p><strong>Results: </strong>Overall, we found no difference in complication rates, emergency department visits, and postoperative admissions when comparing outpatient PCNL to inpatient PCNL, and to previously published statistics for inpatient PCNL. Some studies even showed lower rates of adverse outcomes in ambulatory cohorts when compared to inpatient cohorts. Additionally, ambulatory PCNL conferred significant healthcare savings over inpatient PCNL.</p><p><strong>Conclusion: </strong>This literature review suggests that ambulatory PCNL can be safely performed in both optimal and suboptimal surgical candidates with no significant increase in complications. Additional high-quality studies are warranted to further the evidence surrounding outpatient PCNL and its outcomes.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"12 1","pages":"8-17"},"PeriodicalIF":1.2,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The use of beta-sitosterol for the treatment of prostate cancer and benign prostatic hyperplasia.","authors":"Jill A Macoska","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Herbal supplements are widely used to enhance prostate health. These supplements may contain several types of plant sterols, vitamins, and minerals. By weight, however, plant sterols make up an abundant ingredient component, with saw palmetto extract or its primary component, beta-sitosterol, often comprising the most abundant sterol. Saw palmetto extract/beta-sitosterol has been shown to promote anti-tumorigenic processes in prostate cancer cells and rodent models of prostate cancer. It has also been shown to inhibit the 5α-reductase enzyme, thereby behaving similarly to finasteride and dutasteride, which are widely used to treat prostatic enlargement, or benign prostatic hyperplasia (BPH). The aim of this study is to critically examine <i>in vitro</i>, <i>in vivo</i>, and human clinical studies to assess the safety and clinical utility of herbal supplements containing saw palmetto extract/beta-sitosterol for prostate health. The results of this study suggest multiple mechanisms through which beta-sitosterol represses prostate cancer <i>in vitro</i> and <i>in vivo</i>, particularly through its pro-apoptotic effect on prostate epithelial cells. Multiple studies also show that beta-sitosterol significantly improves lower urinary tract symptoms (LUTS) associated with BPH, but to an extent that is generally less effective than that achieved by pharmaceutical grade alpha-adrenergic receptor antagonists or 5α-reductase inhibitors. This latter finding suggests that supplements containing beta-sitosterol might be most appropriate for younger men with minimal LUTS who don't wish to embark on a clinical drug regimen for BPH treatment.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 6","pages":"467-480"},"PeriodicalIF":1.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oxana Shatkovskaya, Dilyara Kaidarova, Bakytzhan Ongarbayev, Madina Sagi, Ilya Tsimafeyeu
{"title":"Five-year overall survival of patients with advanced bladder cancer in Kazakhstan: OSURK registry study.","authors":"Oxana Shatkovskaya, Dilyara Kaidarova, Bakytzhan Ongarbayev, Madina Sagi, Ilya Tsimafeyeu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>The goals of the OSURK registry study were to assess 5-year overall survival (OS) in patients with metastatic urothelial cancer diagnosed in 2017 in Kazakhstan and collect data on the use of various treatment options in routine clinical practice.</p><p><strong>Methods: </strong>Patients with newly diagnosed metastatic bladder cancer (BC) were retrospectively identified in the national register of Kazakhstan (ERCP) between January 2017 and January 2018. ERCP is the biggest register in the country and includes patient data from 17 regions. Investigators collected patient information and processed records online on the following anonymised data: demographical characteristics, received treatment and outcomes. Patients were included in the study if mBC was confirmed histologically and they had at least one visit to the cancer center during the follow-up period. The outcomes of interest were overall survival (OS), patient characteristics and treatment patterns.</p><p><strong>Results: </strong>Totally 480 adult patients with metastatic BC were included. Mean number of patients in one region per year was 28.2. Median age at diagnosis of mBC was 70.0 years (range, 30-100). Patients were predominantly male (81.3%), histological subtype of BC (urothelial carcinoma, etc.) was determined in 41%. Overall, 187 (39%) patients received systemic therapy for metastatic disease. Platinum-based chemotherapy was prescribed in 147 (76.8%) patients who received systemic treatment. The majority of treatment was with cisplatin (N=132, 70.6%). Sixty-four (13.3%) patients received ≥2 treatment lines. After median 60.5 months of follow-up the 5-year OS in patients with metastatic BC was 2.7%. The 1-, and 3-year OS rates were 31.0% and 9.8%, respectively. Median OS from the start of treatment was 7.3 months (95% CI 6.5-8.1).</p><p><strong>Conclusions: </strong>The results of the OSURK study indicate the need for further implementation of innovative drugs in real practice in order to significantly increase the OS of patients with metastatic BC.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 6","pages":"542-548"},"PeriodicalIF":1.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christy Charles, Stacy M Lloyd, Danthasinghe Waduge Badrajee Piyarathna, Jie Gohlke, Uttam Rasaily, Vasanta Putluri, Brian W Simons, Alexander Zaslavsky, Srinivas Nallandhighal, George Michailidis, Nallasivam Palanisamy, Nora Navone, Jeffrey A Jones, Michael M Ittmann, Nagireddy Putluri, David R Rowley, Simpa S Salami, Ganesh S Palapattu, Arun Sreekumar
{"title":"Role of adenosine deaminase in prostate cancer progression.","authors":"Christy Charles, Stacy M Lloyd, Danthasinghe Waduge Badrajee Piyarathna, Jie Gohlke, Uttam Rasaily, Vasanta Putluri, Brian W Simons, Alexander Zaslavsky, Srinivas Nallandhighal, George Michailidis, Nallasivam Palanisamy, Nora Navone, Jeffrey A Jones, Michael M Ittmann, Nagireddy Putluri, David R Rowley, Simpa S Salami, Ganesh S Palapattu, Arun Sreekumar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostate cancer (PCa) is the second most common cancer and constitutes about 14.7% of total cancer cases. PCa is highly prevalent and more aggressive in African-American (AA) men than in European-American (EA) men. PCa tends to be highly heterogeneous, and its complex biology is not fully understood. We use metabolomics to better understand the mechanisms behind PCa progression and disparities in its clinical outcome. Adenosine deaminase (ADA) is a key enzyme in the purine metabolic pathway; it was found to be upregulated in PCa and is associated with higher-grade PCa and poor disease-free survival. The inosine-to-adenosine ratio, which is a surrogate for ADA activity was high in PCa patient urine and higher in AA PCa compared to EA PCa. To understand the significance of high ADA in PCa, we established ADA overexpression models and performed various <i>in vitro</i> and <i>in vivo</i> studies. Our studies have revealed that an acute increase in ADA expression during later stages of tumor development enhances <i>in vivo</i> growth in multiple pre-clinical models. Further analysis revealed that mTOR signaling activation could be associated with this tumor growth. Chronic ADA overexpression shows alterations in the cells' adhesion machinery and a decrease in cells' ability to adhere to the extracellular matrix <i>in vitro</i>. Losing cell-matrix interaction is critical for metastatic dissemination which suggests that ADA could potentially be involved in promoting metastasis. This is supported by the association of higher ADA expression with higher-grade tumors and poor patient survival. Overall, our findings suggest that increased ADA expression may promote PCa progression, specifically tumor growth and metastatic dissemination.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 6","pages":"594-612"},"PeriodicalIF":1.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kiana L Holbrook, Sabur Badmos, Ahsan Habib, Elizabeth Noriega Landa, George E Quaye, Michael Pokojovy, Xiaogang Su, Wen-Yee Lee
{"title":"Investigating the effects of storage conditions on urinary volatilomes for their reliability in disease diagnosis.","authors":"Kiana L Holbrook, Sabur Badmos, Ahsan Habib, Elizabeth Noriega Landa, George E Quaye, Michael Pokojovy, Xiaogang Su, Wen-Yee Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Cancer detection presents challenges regarding invasiveness, cost, and reliability. As a result, exploring alternative diagnostic methods holds significant clinical importance. Urinary metabolomic profiling has emerged as a promising avenue; however, its application for cancer diagnosis may be influenced by sample preparation or storage conditions.</p><p><strong>Objective: </strong>This study aimed to assess the impact of sample storage and processing conditions on urinary volatile organic compounds (VOCs) profiles and establish a robust standard operating procedure (SOP) for such diagnostic applications.</p><p><strong>Methods: </strong>Five key variables were investigated: storage temperatures, durations, freeze-thaw cycles, sample collection conditions, and sample amounts. The analysis of VOCs involved stir bar sorptive extraction coupled with thermal desorption-gas chromatography/mass spectrometry (SBSE-TD-GC-MS), with compound identification facilitated by the National Institute of Standards and Technology Library (NIST). Extensive statistical analysis, including combined scatterplot and response surface (CSRS) plots, partial least squares-discriminant analysis (PLS-DA), and probability density function plots (PDFs), were employed to study the effects of the factors.</p><p><strong>Results: </strong>Our findings revealed that urine storage duration, sample amount, temperature, and fasting/non-fasting sample collection did not significantly impact urinary metabolite profiles. This suggests flexibility in urine sample collection conditions, enabling individuals to contribute samples under varying circumstances. However, the influence of freeze-thaw cycles was evident, as VOC profiles exhibited distinct clustering patterns based on the number of cycles. This emphasizes the effect of freeze-thaw cycles on the integrity of urinary profiles.</p><p><strong>Conclusions: </strong>The developed SOP integrating SBSE-TD-GC-MS and statistical analyses can serve as a valuable tool for analyzing urinary organic compounds with minimal preparation and sensitive detection. The findings also support that urinary VOCs for cancer screening and diagnosis could be a feasible alternative offering a robust, non-invasive, and sensitive approach for cancer screening.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 6","pages":"481-499"},"PeriodicalIF":1.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neurobiological insights into lower urinary tract dysfunction: evaluating the role of brain-derived neurotrophic factor.","authors":"Chen Cheng, Qingfeng Li, Guiting Lin, Emmanuel C Opara, Yuanyuan Zhang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Lower urinary tract dysfunction (LUTD) encompasses a range of debilitating conditions that affect both sexes and different age groups. Understanding the underlying neurobiological mechanisms contributing to LUTD has emerged as a critical avenue for the development of targeted therapeutic strategies. Brain-derived neurotrophic factor (BDNF), a prominent member of the neurotrophin family, has attracted attention due to its multiple roles in neural development, plasticity, and maintenance. This review examines the intricate interplay between neurobiological factors and LUTD, focusing on the central involvement of BDNF. The review emphasizes the bidirectional relationship between LUTD and BDNF and explores how LUTD-induced neural changes may affect BDNF dynamics and vice versa. Growth factor therapy and the combined administration of controlled release growth factors and stem cells are minimally invasive treatment strategies for neuromuscular injury. Among the many growth factors and cytokines, brain-derived neurotrophic factor (BDNF) plays a prominent role in neuromuscular repair. As an essential neurotrophin, BDNF is involved in the modulation of neuromuscular regeneration through tropomyosin receptor kinase B (TrkB). Increasing BDNF levels facilitates the regeneration of the external urethral sphincter and contributes to the regulation of bladder contraction. Treatments targeting the BDNF pathway and sustained release of BDNF may become novel treatment options for urinary incontinence and other forms of lower urinary tract dysfunction. This review discusses the applications of BDNF and the theoretical basis for its use in the treatment of lower urinary tract dysfunction, including urinary incontinence (UI), overactive bladder (OAB), and benign prostatic hyperplasia (BPH), and in the clinical diagnosis of bladder dysfunction.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 6","pages":"559-577"},"PeriodicalIF":1.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhina Sadeghi, Yi Xi Wu, Amberly Vu, Liankun Song, William Phan, Jeffery Kim, Janet R Keast, Ulysses Balis, John DeLancey, S Armando Villalta, Xiaolin Zi
{"title":"Dysfunction of the aging female mouse urethra is associated with striated muscle loss and increased fibrosis: an initial report.","authors":"Zhina Sadeghi, Yi Xi Wu, Amberly Vu, Liankun Song, William Phan, Jeffery Kim, Janet R Keast, Ulysses Balis, John DeLancey, S Armando Villalta, Xiaolin Zi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The decline of urethral function with advancing age plays a major role in urinary incontinence in women, impairing quality of life and economically burdening the health care system. However, none of the current urinary incontinence treatments address the declining urethral function with aging, and the mechanisms by which aging impacts urethra physiology remain little known or explored. Here, we have compared functional, morphometric, and global gene expression of urethral tissues between young and old female mice. Bladder leak point pressure (LPP) measurement showed that the aged female mice had 26.55% lower LPP compared to younger mice. Vectorized Scale-Invariant Pattern Recognition (VIPR) analysis of the relative abundance of different tissue components revealed that the mid-urethra of old female mice contains less striated muscle, more extracellular matrix/fibrosis, and diminished elastin fibers ratio compared to young mice. Gene expression profiling analysis (bulk RNA-seq of the whole urethra) showed more down-regulated genes in aged than young mice. Immune response and muscle-related (striated and smooth) pathways were predominantly enriched. In contrast, keratinization, skin development, and cell differentiation pathways were significantly downregulated in aged urethral tissues compared to those from young female mice. These results suggest that molecular pathways (<i>i.e.</i>, ACVR1/FST signaling and CTGF/TGF-β signaling) leading to a decreased striated muscle mass and an increase in fibrous extracellular matrix in the process of aging deserve further investigation for their roles in the declined urethral function.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 6","pages":"516-529"},"PeriodicalIF":1.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mary M Stangis, Avan N Colah, Dalton T McLean, Richard B Halberg, Lara S Collier, William A Ricke
{"title":"Potential roles of FGF5 as a candidate therapeutic target in prostate cancer.","authors":"Mary M Stangis, Avan N Colah, Dalton T McLean, Richard B Halberg, Lara S Collier, William A Ricke","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Fibroblast growth factor (FGF) is a secreted ligand that is widely expressed in embryonic tissues but its expression decreases with age. In the developing prostate, FGF5 has been proposed to interact with the Hedgehog (Hh) signaling pathway to guide mitogenic processes. In the adult prostate, the FGF/FGFR signaling axis has been implicated in prostate carcinogenesis, but focused studies on FGF5 functions in the prostate are limited. Functional studies completed in other cancer models point towards FGF5 overexpression as an oncogenic driver associated with stemness, metastatic potential, proliferative capacity, and increased tumor grade. In this review, we explore the significance of FGF5 as a therapeutic target in prostate cancer (PCa) and other malignancies; and we introduce a potential route of investigation to link FGF5 to benign prostatic hyperplasia (BPH). PCa and BPH are two primary contributors to the disease burden of the aging male population and have severe implications on quality of life, psychological wellbeing, and survival. The development of new FGF5 inhibitors could potentially alleviate the health burden of PCa and BPH in the aging male population.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 6","pages":"452-466"},"PeriodicalIF":1.5,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hua Huang, Shiqi Song, Wang Liu, Sudan Ye, Yonghua Bao, Moben Mirza, Benyi Li, Jian Huang, Runzhi Zhu, Huibo Lian
{"title":"Expressions of glucose transporter genes are diversely attenuated and significantly associated with prostate cancer progression.","authors":"Hua Huang, Shiqi Song, Wang Liu, Sudan Ye, Yonghua Bao, Moben Mirza, Benyi Li, Jian Huang, Runzhi Zhu, Huibo Lian","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostate cancer is a health-threaten disease in men worldwide, however, lacking is the reliable biomarkers for patient management. Aberrant metabolic events including glucose metabolism are involved in prostate cancer progression. To examine the involvement of glucose metabolic pathways in prostate cancer, we analyzed the expression profiles of glucose transporter family genes using multiple RNA-seq datasets. Our results showed that three SLC2A family genes (SLC2A4/5/9) were significantly downregulated in primary prostate cancers compared to their benign compartments. These down-regulated expressions were inversely correlated with their gene promoter methylation and genome abnormalities. Among these three SLC2A genes, only SLC2A4 showed a significantly reverse correlation with all clinicopathological parameters, including TNM stage, disease relapse, Gleason score, disease-specific survival, and progression-free interval. In addition, the expression levels of these three genes were strongly correlated with anti-cancer immune cell filtration in primary prostate cancers. In a group of patients with early-onset prostate cancers, SLC2A4 also showed a strong negative correlation with multiple clinicopathological parameters, such as tumor mutation burden, biochemical relapse, pre-surgical PSA levels, and Gleason score but a positive correlation with progression-free interval after surgery. In metastatic castration-resistant prostate cancers (CRPC), SLC2A9 gene expression but not SLC2A4 or SLC2A5 genes showed a significant correlation with androgen receptor (AR) activity score and neuroendocrinal (NE) activity score. Meanwhile, SLC2A2/9/13 expression was significantly elevated in CRPC tumors with neuroendocrinal features compared to those without NE features. On the other hand, SLC2A10 and SlC2A12 gene expression were significantly reduced in NEPC tumors compared to CRPC tumors. Consistently, SLC2A10/12 expression levels were significantly reduced in castrated animals carrying the LuCaP35 xenograft models. Survival outcome analysis revealed that SLC2A4 expression in primary tumors is a favorable prognostic factor and SLC2A6 is a worse prognostic factor for disease-specific survival and progression-free survival in prostate cancer patients. In conclusion, our results suggest that SLC2A4/6 expressions are strong prognostic factors for prostate cancer progression and survival. The significance of SLC2A2/9/13 over-expression during NEPC progression needs more investigation.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 6","pages":"578-593"},"PeriodicalIF":1.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}