Ewelina Zarakowska, Jolanta Guz, Daniel Gackowski, Ryszard Olinski
{"title":"Relationship Between Prostate Cancer and Benign Hyperplasia: Role of Inflammation-Induced Oxidative Stress, Vitamin C, and Epigenetics.","authors":"Ewelina Zarakowska, Jolanta Guz, Daniel Gackowski, Ryszard Olinski","doi":"10.5534/wjmh.250116","DOIUrl":"https://doi.org/10.5534/wjmh.250116","url":null,"abstract":"<p><p>Benign prostatic hyperplasia and prostate cancer (PC) frequently affect aging men, both involving irregular cell growth in the prostate. Inflammation is a major contributor to these conditions, whereas DNA methylation and hydroxymethylation are specifically involved in PC development. In this review, we address several potential factors influencing the progression of PC, including DNA epigenetic marks, ascorbate (vitamin C) concentration in the blood plasma, and its intracellular levels in leukocytes and prostate tissues. Moreover, a new aspect concerning the involvement of leukocytes (white blood cells) in PC formation will also be discussed, highlighting their potential utility for assessing early PC development through a minimally invasive approach.</p>","PeriodicalId":54261,"journal":{"name":"World Journal of Mens Health","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144978685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brian Ng Hung Shin, Rebekah Maksoud, Samuel Tan, Handoo Rhee, Hyun Jun Park, Eric Chung
{"title":"Efficacy and Tolerability Outcomes of Minimally Invasive Surgical Treatments for Benign Prostatic Hyperplasia: A Random-Effects Network Meta-Analysis.","authors":"Brian Ng Hung Shin, Rebekah Maksoud, Samuel Tan, Handoo Rhee, Hyun Jun Park, Eric Chung","doi":"10.5534/wjmh.250092","DOIUrl":"https://doi.org/10.5534/wjmh.250092","url":null,"abstract":"<p><strong>Purpose: </strong>Minimally invasive surgical treatments (MIST) provide emerging alternatives to transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH). This network meta-analysis provides a comparative analysis of clinical efficacy and tolerability for individual MIST versus TURP in BPH.</p><p><strong>Materials and methods: </strong>A PRISMA-compliant systematic review was performed by searching the PubMed, EMBASE, and Cochrane Library databases from inception to 31 August 2023. Eligible studies compared post-treatment change scores or relative risks between ≥2 distinct BPH interventions for International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), post-void residual urine, Sexual Health Inventory in Men (SHIM) and Men's Sexual Health Questionnaire (MSHQ) scores, and re-intervention rate. Pairwise comparisons were synthesized through a random-effects frequentist model to determine aggregate estimates for treatment-outcome associations.</p><p><strong>Results: </strong>Of 4,416 screened articles, 59 studies were included for quantitative analysis, comprising 21,078 patients across 47 unique cohorts. Prostatic arterial embolization (PAE) and Aquablation appeared to induce similar reductions in IPSS to TURP; however, there was insufficient data to evaluate the tolerability of PAE or Aquablation. Water vapor thermal therapy (WVTT) and prostatic urethral lift (PUL) were less efficacious at reducing IPSS than TURP but exhibited greater preservation of SHIM and MSHQ scores. TURP demonstrated the lowest relative risk of re-intervention.</p><p><strong>Conclusions: </strong>PAE and Aquablation appear to be efficacious approaches to BPH management, with PAE also producing a comparable increase in Qmax to TURP. WVTT and PUL appear less effective than TURP but are associated with lower risk of male sexual dysfunction.</p>","PeriodicalId":54261,"journal":{"name":"World Journal of Mens Health","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prostate Cancer at the Microbial Crossroads: Illuminating a New Frontier in Precision Medicine.","authors":"Whi-An Kwon, Heeyeon Kim, Yong Sang Song","doi":"10.5534/wjmh.250045","DOIUrl":"https://doi.org/10.5534/wjmh.250045","url":null,"abstract":"<p><p>The human body harbors a complex, dynamic community of trillions of microbes, collectively termed the microbiota, which profoundly affects homeostasis and disease processes, including cancer. Prostate cancer remains a major cause of morbidity and mortality among men worldwide; however, critical questions remain regarding its etiology, progression, and resistance to therapy. Multiple epidemiological studies have found associations between certain urinary and intestinal microorganisms and an increased prostate cancer risk, although the causal mechanisms remain incompletely understood. Recent studies suggest that dysregulated microbial communities, or dysbiosis, are hypothesized to drive chronic inflammation, induce genotoxic insults, and modulate steroid metabolism, thereby influencing tumor initiation and progression. Conflicting findings across different investigations often stem from heterogeneous sampling methods, population differences, and disparate bioinformat ics pipelines, underscoring the critical need for standardized protocols and reproducible data analytics. For example, diet induced alterations in the gut microbiota can shift systemic inflammatory and hormonal pathways in ways that predispose individuals to malignant transformation. Simultaneously, prostatic and urinary microbes are hypothesized to fuel local inflam mation and promote precursor lesions, although whether this microbial activity is causative or merely reflective of the exist ing tumor biology remains a key unresolved question. Microbiota-driven mechanisms also shape responses to radiotherapy, chemotherapy, and emerging immunotherapies, highlighting the potential of interventions such as probiotics, prebiotics, and fecal microbiota transplantation to enhance treatment efficacy and mitigate side effects. Innovative approaches, including ar tificial intelligence-assisted predictive modeling, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based microbial gene editing, and immunomodulatory strategies (e.g., chimeric antigen receptor-T cells), offer new avenues for exploiting microbiota for therapeutic benefits. Nevertheless, unresolved questions regarding the long-term safety, ecological balance, and individual patient factors require caution. By integrating rigorous methodologies with these novel technologies, prostate cancer research may ultimately harness microbial insights to refine diagnostic tools, personalize therapies, and im prove patient outcomes.</p>","PeriodicalId":54261,"journal":{"name":"World Journal of Mens Health","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie Alexandra Edison, Michael Kirby, Geoffrey Ian Hackett
{"title":"Testosterone Replacement Therapy in Hypogonadal Men with a Prostate Cancer Diagnosis: A British Society for Sexual Medicine Consensus Statement.","authors":"Marie Alexandra Edison, Michael Kirby, Geoffrey Ian Hackett","doi":"10.5534/wjmh.250086","DOIUrl":"https://doi.org/10.5534/wjmh.250086","url":null,"abstract":"<p><p>Hypogonadism in men with a history of prostate cancer presents a complex clinical challenge, with longstanding concerns that testosterone replacement therapy (TRT) could potentially stimulate cancer recurrence or progression. This paper provides an up-to-date review of the evidence on the safety and efficacy of TRT, focusing on its use in key clinical scenarios such as active surveillance, post-radical prostatectomy, and post-radiotherapy. We examine the latest data on oncological safety, including risks of disease progression and biochemical recurrence, alongside the benefits of TRT in addressing hypogonadal symptoms such as fatigue, mood disturbance, and sexual dysfunction. The discussion also considers how TRT safety aligns with advancements in prostate cancer biology, including the saturation model, and how these insights are reflected in guidelines from major organisations such as the British Society for Sexual Medicine (BSSM), American Urological Association (AUA), and European Association of Urology (EAU). Gaps in long-term data and areas for further research are identified, underscoring the need for careful application in clinical practice. This paper emphasises a multidisciplinary approach in patient selection, rigorous monitoring protocols, and fully informed decision-making. By presenting a comprehensive review of the evidence, we aim to clarify the role of TRT in improving quality of life for men in remission from prostate cancer, while ensuring that oncological safety remains the highest priority.</p>","PeriodicalId":54261,"journal":{"name":"World Journal of Mens Health","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of a Novel Biallelic <i>CFAP119</i> Variant in an Infertile Man with Asthenoteratozoospermia.","authors":"Jun Ma, Tiechao Ruan, Chuan Jiang, Xiang Wang, Yingteng Zhang, Yunchuan Tian, Xinyao Tang, Yihong Yang, Ying Shen","doi":"10.5534/wjmh.240269","DOIUrl":"https://doi.org/10.5534/wjmh.240269","url":null,"abstract":"<p><strong>Purpose: </strong>Infertility affects approximately 10% to 20% of couples globally, with male factors contributing to nearly 50% of infertility cases. Among these, represents a severe form of male infertility, though its etiology remains largely unknown. CFAP119 has been implicated in sperm flagellar formation and is essential for fertility in mice; however, its role in human fertility has not been established.</p><p><strong>Materials and methods: </strong>Whole exome sequencing (WES) was performed to identify pathogenic variants in a patient with asthenoteratozoospermia, and the functional impact of the mutations was assessed using <i>in silico</i> and <i>in vitro</i> analysis. Intracytoplasmic sperm injection (ICSI) was applied to assist fertilization for the patient.</p><p><strong>Results: </strong>In this study, we identified a novel biallelic missense mutation in <i>CFAP119</i> in a patient with asthenoteratozoospermia through WES. Immunofluorescence staining and western blotting demonstrated that the variants impaired the protein expression. Morphological analysis of the patient's sperm revealed severely malformed tails and head abnormalities. Ultrastructural examination also confirmed significant defects in the sperm flagella \"9+2\" microtubule composition. Additionally, <i>in silico</i> analysis predicted interactions between CFAP119 and flagellum development related proteins, including CFAP74, CFAP221, which were further validated by co-immunoprecipitation. Notably, the patient with the <i>CFAP119</i> mutation successfully achieved healthy offspring through ICSI.</p><p><strong>Conclusions: </strong>Our findings revealed novel pathogenic variants within <i>CFAP119</i> in patient with asthenoteratozoospermia, expanding our understanding of the genetic etiology of male infertility and providing valuable insights for future diagnostic and therapeutic approaches.</p>","PeriodicalId":54261,"journal":{"name":"World Journal of Mens Health","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sung Chul Kam, Yu Seob Shin, Doo Sang Kim, Won Ki Lee, Deok Hyun Han, Phil Hyun Song, Sung Hoo Hong, Young Seop Chang, Tae Hwan Kim, Sung Tae Cho, Sung Yul Park, Jae Hyun Bae, Kyung Jin Chung, Joon Hwa Noh, Kang Su Cho, Tae Nam Kim, Zhao Luo, Won Sik Ham, Tae Hyo Kim
{"title":"Efficacy and Safety of Mirabegron and Tamsulosin Combination Therapy Compared to Tamsulosin Monotherapy for Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: Results of a Multicenter, Randomized, Double-Blind, Phase III Clinical Trial.","authors":"Sung Chul Kam, Yu Seob Shin, Doo Sang Kim, Won Ki Lee, Deok Hyun Han, Phil Hyun Song, Sung Hoo Hong, Young Seop Chang, Tae Hwan Kim, Sung Tae Cho, Sung Yul Park, Jae Hyun Bae, Kyung Jin Chung, Joon Hwa Noh, Kang Su Cho, Tae Nam Kim, Zhao Luo, Won Sik Ham, Tae Hyo Kim","doi":"10.5534/wjmh.250085","DOIUrl":"https://doi.org/10.5534/wjmh.250085","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the efficacy and safety of mirabegron and tamsulosin combination therapy compared to tamsulosin monotherapy in benign prostatic hyperplasia (BPH) patients with lower urinary tract symptoms (LUTS).</p><p><strong>Materials and methods: </strong>This phase 3, randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy and safety of mirabegron/tamsulosin combination therapy versus tamsulosin monotherapy in men with LUTS. The trial, conducted across 25 centers from July 2021 to October 2023. Eligible participants were randomly assigned to either the combination or monotherapy group for 12 weeks. Primary efficacy endpoints included changes in total urinary frequency score (TUFS) and International Prostate Symptom Scores (IPSS), with secondary endpoints evaluating various urinary symptoms and changes in post void residual volume (PVR), maximum urinary flow rate (Qmax), and quality of life scores. Safety assessments included adverse events, PVR, Qmax, vital signs, electrocardiogram, and laboratory tests.</p><p><strong>Results: </strong>A total of 795 participants were randomized to monotherapy (n=397) and combination therapy (n=398) groups. After 12 weeks, 342 in the monotherapy and 339 in the combination therapy group completed the study, with no significant baseline differences. The combination therapy group showed a greater improvement in TUFS (-11.28) and IPSS (-10.85) scores compared to monotherapy (-8.30 and -9.85, respectively) with significant differences (p<0.0001, p=0.0325). Combination therapy showed significant improvements in storage symptoms and voiding diary variables, including daytime frequency, urgency, and incontinence, compared to monotherapy. The incidence of treatment-emergent adverse events was similar between the groups (13.10% <i>vs</i> 16.58%, p=0.1943), with no serious drug-related adverse events, confirming an acceptable safety profile for combination therapy.</p><p><strong>Conclusions: </strong>Combination therapy with mirabegron and tamsulosin is more effective than monotherapy in improving LUTS in patients with BPH, particularly storage symptoms, with a comparable safety profile. A fixed-dose combination formulation in the future may further improve patient adherence and quality of life.</p>","PeriodicalId":54261,"journal":{"name":"World Journal of Mens Health","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liangyou Chen, Zhang Chen, Xu Zheng, Jie Wu, Zaisheng Zhu
{"title":"Causal Relationship Between Dietary-Derived Antioxidants and Erectile Dysfunction: A Mendelian Randomization Study.","authors":"Liangyou Chen, Zhang Chen, Xu Zheng, Jie Wu, Zaisheng Zhu","doi":"10.5534/wjmh.250078","DOIUrl":"https://doi.org/10.5534/wjmh.250078","url":null,"abstract":"<p><strong>Purpose: </strong>Current research suggests a correlation between erectile dysfunction (ED) and dietary-derived antioxidants. However, the causal relationship between these factors remains unclear. This study aims to investigate the causal relationship between dietary-derived antioxidants and ED using Mendelian randomization (MR) analysis, based on genetic prediction.</p><p><strong>Materials and methods: </strong>This study employed bidirectional two-sample MR analysis to investigate the causal relationship between dietary-derived antioxidants and ED. The primary results were based on inverse variance-weighted analysis with random effects. To assess the robustness and reliability of the findings, sensitivity analyses were conducted, including tests for heterogeneity, horizontal pleiotropy, and leave-one-out analysis. Additionally, multivariate MR analysis was performed to further validate the robustness of the results.</p><p><strong>Results: </strong>The inverse variance-weighted results revealed a significant causal relationship between plasma vitamin A levels and ED (odds ratio [OR]: 3.44; 95% confidence interval [95% CI]: 1.22-9.68; p=0.019), suggesting that elevated plasma vitamin A levels are a risk factor for ED. A reverse causal relationship was observed between ED and carotene levels (OR: 0.97, 95% CI: 0.95-1.00; p=0.04). After adjusting for smoking status, the causal association between vitamin A and ED remained significant. The heterogeneity test indicated variability in the relationship between carotene and ED, while the pleiotropy test revealed that the MR-PRESSO p-value for zinc and ED was less than 0.05.</p><p><strong>Conclusions: </strong>This study identifies specific causal relationships between dietary antioxidants and ED, providing a foundation for understanding the pathogenesis of ED, guiding the development of dietary intervention strategies, and informing clinical treatment approaches.</p>","PeriodicalId":54261,"journal":{"name":"World Journal of Mens Health","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Influence of High-Normal Fasting Blood Glucose on Semen Quality, Embryonic Development, and Pregnancy Outcomes.","authors":"Lina Wang, Huanhuan Li, Wenhui Zhou","doi":"10.5534/wjmh.250083","DOIUrl":"https://doi.org/10.5534/wjmh.250083","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the correlation between male high-normal fasting blood glucose (FBG) and semen quality, embryonic development, and pregnancy outcomes of <i>in vitro</i> fertilization (IVF)/intracytoplasmic sperm injection (ICSI).</p><p><strong>Materials and methods: </strong>This retrospective cohort study included 921 couples undergoing their first single blastocyst frozen-thawed embryo transfer cycles. Participants were divided into 4 groups depending on quartiles of male FBG (3.90-6.10 mmol/L): from the lowest Quartile 1 (Q1) to the highest Q4. Firstly, semen quality and reproductive outcomes were compared across groups. Next, based on male FBG quartiles, logistic regression models were performed to explore associations between FBG with semen quality and IVF/ICSI outcomes. Finally, with male FBG considered as continuous variables, generalized additive models (GAMs) were conducted to visualize the non-linear relationship of FBG with the outcomes. Primary outcome: live birth rate (LBR). Secondary outcomes: semen quality, embryonic development parameters, biochemical pregnancy rate (BPR), clinical pregnancy rate, miscarriage rate, and other pregnancy outcomes.</p><p><strong>Results: </strong>Higher FBG quartiles exhibited significantly reduced sperm total motility, progressive motility, and progressive sperm count, alongside increased asthenozoospermia prevalence (p<0.05). BPRs rose from Q1 (4.4%) to Q4 (11.0%) (p=0.033), while LBR showed a declining trend from Q1 (46.7%) to Q4 (36.0%) (p=0.102). Regression analysis indicated that males in Q4 had a higher biochemical pregnancy risk and lower live birth likelihood (p-trend<0.05). GAMs revealed a dose-dependent increase in both asthenozoospermia and biochemical pregnancy risks with rising FBG levels.</p><p><strong>Conclusions: </strong>High-normal male FBG is significantly associated with both impaired semen quality (particularly asthenozoospermia) and adverse IVF/ICSI outcomes, including increased biochemical pregnancy risk and reduced LBRs. These findings highlight the significance of assessing paternal metabolic health and suggest that FBG screening may serve as a valuable tool for optimizing IVF/ICSI strategies and improving reproductive success.</p>","PeriodicalId":54261,"journal":{"name":"World Journal of Mens Health","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiun-Hung Geng, Chia-Cheng Yu, Chao-Yuan Huang, Victor C Lin, Chia-Yang Li, Ming-Tsang Wu, Szu-Chia Chen, Bo-Ying Bao, Shu-Pin Huang
{"title":"Development and Validation of a Genome-Wide Association Study Based Polygenic Risk Score for Prostate Cancer in an Asian Population.","authors":"Jiun-Hung Geng, Chia-Cheng Yu, Chao-Yuan Huang, Victor C Lin, Chia-Yang Li, Ming-Tsang Wu, Szu-Chia Chen, Bo-Ying Bao, Shu-Pin Huang","doi":"10.5534/wjmh.250056","DOIUrl":"https://doi.org/10.5534/wjmh.250056","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to estimate genetic susceptibility to prostate cancer (PCa) by constructing a polygenic risk score (PRS) using single nucleotide polymorphisms (SNPs) identified from genome-wide association studies.</p><p><strong>Materials and methods: </strong>The study included 1,015 PCa patients from our institutions and 1,015 age-matched controls from the Taiwan Biobank (TWB). An independent external validation cohort of 188 PCa patients and 188 TWB controls (excluding those from the primary cohort) was assembled. DNA was extracted from blood samples, with approximately 690,000 SNPs genotyped (minor allele frequency ≥0.05) and 15 million additional SNPs imputed using the 1000 Genomes Project. After quality control, 958 PCa patients and 999 controls were included in the analysis. The PRS was developed using PRSice2 by dividing samples into a base dataset and a model-testing set. Model performance was assessed using receiver operating characteristic analysis and cross-validation (CV).</p><p><strong>Results: </strong>Of the 87,092 SNPs initially considered, 24 were used to construct the PRS, located in intronic regions of genes such as <i>KCNH7</i>, <i>HLA-DQA1</i>, and <i>PRNCR1</i>. The PRS significantly improved PCa prediction, achieving an area under the curve (AUC) of 0.824 (p=1.23×10⁻⁵⁰). Patients in the top 25th percentile of PRS had a 34-fold higher risk compared to those in the bottom 25th percentile (odds ratio=34.37, 95% confidence interval=22.93-51.68, p=1.96×10⁻⁵². The model showed stable performance with mean accuracies of 0.75 (3-fold CV) and 0.76 (10-fold CV) and achieved an AUC of 0.757 in the independent validation cohort.</p><p><strong>Conclusions: </strong>The developed PRS showed robust predictive ability for PCa in the Taiwanese population and may inform future risk stratification and personalized interventions.</p>","PeriodicalId":54261,"journal":{"name":"World Journal of Mens Health","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chin-Hee Song, Yonghoon Choi, Nayoung Kim, Ryoung Hee Nam, Jin Won Kim, Jae Young Jang, Eun Hye Kim, Sungchan Ha, Ha-Na Lee
{"title":"Differential NRF2 Methylation and PD-1 Expression in Normal Tissues of Colorectal Adenoma and Carcinoma across Sexes.","authors":"Chin-Hee Song, Yonghoon Choi, Nayoung Kim, Ryoung Hee Nam, Jin Won Kim, Jae Young Jang, Eun Hye Kim, Sungchan Ha, Ha-Na Lee","doi":"10.5534/wjmh.250061","DOIUrl":"https://doi.org/10.5534/wjmh.250061","url":null,"abstract":"<p><strong>Purpose: </strong>Metachronous cancer following the cure of the primary cancer could be related with the tumor microenvironment. Recently it has been known that nuclear factor erythroid 2-related factor 2 (<i>NRF2</i>), a key transcription factor regulates immune checkpoint expression, including programmed cell death-ligand 1 (PD-L1), a well-known checkpoint molecule. The aim of this study was to investigate the roles of <i>NRF2</i> and <i>PD-1</i> in the tumor microenvironment using the normal colon tissue, with a focus on sex-specific differences.</p><p><strong>Materials and methods: </strong>A total of 280 participants were enrolled including 66 healthy controls (HC), 109 patients with colorectal adenoma (AD), and 105 patients with colorectal cancer (CRC). Quantitative real-time polymerase chain reaction (PCR) for <i>NRF2</i> and <i>PD-1</i> and methylation-specific PCR for <i>NRF2</i> were performed with normal mucosal tissue above the 20 cm from anal verge.</p><p><strong>Results: </strong><i>NRF2</i> methylation levels were significantly lower in the AD and CRC groups compared to the HC in both sexes. <i>PD-1</i> mRNA expression was significantly reduced in the AD and CRC groups compared to the HC group. In terms of sex males showed significantly lower <i>PD-1</i> mRNA levels in the AD and CRC groups, whereas females displayed significantly higher <i>PD-1</i> expression in the AD group but significantly lower levels in the CRC group. In conclusion there were significant differences in <i>NRF2</i> methylation and <i>PD-1</i> expression in the normal mucosal tissue among CRC, AD, and HC groups, suggesting that metachronous lesions might arise from this underlying tumor microenvironment.</p><p><strong>Conclusions: </strong>Our results suggest that mRNA expressions of <i>NRF2</i> and <i>PD-L1</i> in the normal colon tissue may serve as early molecular markers in colorectal carcinogenesis with distinct sex-specific patterns.</p>","PeriodicalId":54261,"journal":{"name":"World Journal of Mens Health","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}