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1.
Aging Male ; 27(1): 2419853, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39460452

RESUMO

BACKGROUND: We aimed to use Mendelian randomization (MR) to determine the causality between fifteen major mental disorders (MDs) and benign prostatic hyperplasia (BPH), prostate cancer (PCa), and prostatitis. METHODS: The main MR analysis was performed using the inverse variance-weighted (IVW) method. RESULTS: The study found that insomnia (odds ratio [OR], 1.6190; p = .0017) was significantly associated with an increased risk of BPH, and mood disorders (OR, 1.1590; p = .0221) was nominally associated with an increased risk of BPH. Conversely, BPH was suggestively associated with a low epilepsy risk (OR, 0.9988; p = .0043), and was nominally associated with an increased risk of insomnia (OR, 1.0061; p = .0291). Furthermore, attention deficit hyperactivity disorder (ADHD) was suggestively associated with a low PCa risk (OR = 0.9474; p = .0058). However, no causal relationship was observed between PCa and MDs. Finally, anorexia nervosa (OR, 1.1686; p = .0248) and depression (OR, 336.5383; p = .0308) were nominally positively correlated with prostatitis. Prostatitis was suggestively associated with increased risk of ADHD (OR, 1.0868; p = .0413). CONCLUSION: Our findings provide clinicians with a basis for developing programs to prevent or treat MDs and prostatic diseases.


Assuntos
Análise da Randomização Mendeliana , Transtornos Mentais , Hiperplasia Prostática , Neoplasias da Próstata , Prostatite , Humanos , Masculino , Prostatite/complicações , Hiperplasia Prostática/genética , Hiperplasia Prostática/complicações , Hiperplasia Prostática/epidemiologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/epidemiologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/genética , Fatores de Risco
2.
Geriatr Nurs ; 58: 304-309, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865784

RESUMO

BACKGROUND: Research has demonstrated that social isolation and loneliness are linked to functional disability in older adults. With the intensification of global aging, functional disability and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) have become common public health issues affecting elderly men. METHODS: This study utilized data from the CHARLS database. The functional status of participants was evaluated through activities of daily living (ADL) and instrumental activities of daily living (IADL). Logistic regression analyses were employed to investigate variables associated with LUTS/BPH. RESULTS: Univariate logistic regression revealed associations between loneliness (OR: 1.26; 95 % CI: 1.08-1.46) (excluding social isolation), ADL (OR: 2.17; 95 % CI: 1.86-2.52), IADL disability (OR: 1.37; 95 % CI: 1.16-1.60), and LUTS/BPH. Following rigorous adjustment for potential confounding factors, it was determined that ADL disability independently correlated with LUTS/BPH (OR: 1.92; 95 % CI: 1.17-3.17). CONCLUSION: ADL disability is significantly linked to an elevated risk of LUTS/BPH in Chinese elderly men. These findings enhance our understanding of the relationship between functional status and LUTS/BPH.


Assuntos
Atividades Cotidianas , Solidão , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/psicologia , Idoso , Sintomas do Trato Urinário Inferior/psicologia , China , Estudos Longitudinais , Solidão/psicologia , Pessoas com Deficiência/psicologia , Aposentadoria , Pessoa de Meia-Idade
3.
Medicine (Baltimore) ; 103(39): e39874, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39331898

RESUMO

PANoptosis has been shown to play an important role in tumorigenesis and gain more attention. Yet, the prognostic significance of PANoptosis-related genes has not been investigated more in clear cell renal cell carcinoma (ccRCC). The aim of this research was designed to identify and create a signature of PANoptosis-related genes which was expected to predict prognosis of ccRCC more effectively. The transcriptome data and clinical information were collected from The Cancer Genome Atlas database and the Gene Expression Omnibus database. Optimal differentially expressed PANoptosis-related genes, which were closely associated with prognosis and employed to construct a risk score, were extracted by univariate Cox analysis, least absolute shrinkage and selection operator Cox regression and multivariate Cox analysis. We performed Kaplan-Meier survival analysis and time-dependent receiver operating characteristic curves to complete this process. By adopting univariate and multivariate analysis, the constructed risk score was assessed to verify whether it could be taken as an independent contributor for prognosis. Moreover, we created a nomogram in order to predict overall survival (OS) of ccRCC. Five differentially expressed PANoptosis-related genes were screened out and used to construct a risk score. Our results showed that ccRCC patients with high risk score had a poor prognosis and shorter OS. The results of Kaplan-Meier curves and the area under the receiver operating characteristic curves of 1-, 3-, and 5-year OS indicated that the prediction performance was satisfactory. Additionally, the risk model could be taken as an independent prognostic factor in training and validation cohorts. The nomogram exhibited excellent reliability in predicting OS, which was validated by calibration curves. We identified 5 PANoptosis-related genes, which were used to construct a risk score and a nomogram for prognostic prediction with reliable predictive capability. The present study may provide new potential therapeutic targets and precise treatment strategies for ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Nomogramas , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Prognóstico , Masculino , Feminino , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Curva ROC , Transcriptoma , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica/métodos
4.
Front Endocrinol (Lausanne) ; 15: 1376800, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715795

RESUMO

Background: Although studies on the effects of diet on fertility has progressed, some cumulative evidence has piled against popular hypotheses. The aim of our study was to investigate the effects of 31 diets including 23 individual dietary intakes and 8 dietary habits on infertility in men and women. Methods: The datas of diets and infertility were collected from genome-wide association studies (GWAS). Mendelian randomization (MR) methods were used to analyze causal relationships. Multivariate MR (MVMR) adjusted for the effects of other exposures on causality. And MR-Egger, Cochran's Q, radial MR, and MR-PRESSO tests were employed to assess heterogeneity and horizontal pleiotropy. Results: Our study found that coffee intake (OR, 3.6967; 95% CI, 1.0348 - 13.2065; P = 0.0442) and cooked vegetable intakes (OR, 54.7865; 95% CI, 2.9011 - 1030.5500; P = 0.0076) increased the risk of male infertility. For women, beer was a risk factor for infertility (OR, 4.0932; 95% CI, 1.8728 - 8.9461; P = 0.0004); but processed meat was negatively associated with infertility (OR, 0.5148; 95% CI, 0.2730 - 0.9705; P = 0.0401). MVMR demonstrated selenium as a protective factor against female infertility (OR, 7.4474e-12; 95% CI, 5.4780e-22 - 1.0125e-01; P = 0.0314). Conclusion: We found the causal relationships between four diets and infertility. We look forward to more high-quality epidemiologic studies to prove our conclusions.


Assuntos
Dieta , Estudo de Associação Genômica Ampla , Infertilidade Feminina , Infertilidade Masculina , Análise da Randomização Mendeliana , Humanos , Feminino , Masculino , Infertilidade Masculina/genética , Infertilidade Masculina/epidemiologia , Infertilidade Masculina/etiologia , Infertilidade Feminina/genética , Infertilidade Feminina/etiologia , Fatores de Risco , Comportamento Alimentar , Adulto , Café/efeitos adversos
5.
Sci Data ; 11(1): 701, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937469

RESUMO

Bone metastasis is an essential factor affecting the prognosis of prostate cancer (PCa), and circulating tumor cells (CTCs) are closely related to distant tumor metastasis. Here, the protein-protein interaction (PPI) networks and Cytoscape application were used to identify diagnostic markers for metastatic events in PCa. We screened ten hub genes, eight of which had area under the ROC curve (AUC) values > 0.85. Subsequently, we aim to develop a bone metastasis-related model relying on differentially expressed genes in CTCs for accurate risk stratification. We developed an integrative program based on machine learning algorithm combinations to construct reliable bone metastasis-related genes prognostic index (BMGPI). On the basis of BMGPI, we carefully evaluated the prognostic outcomes, functional status, tumor immune microenvironment, somatic mutation, copy number variation (CNV), response to immunotherapy and drug sensitivity in different subgroups. BMGPI was an independent risk factor for disease-free survival in PCa. The high risk group demonstrated poor survival as well as higher immune scores, higher tumor mutation burden (TMB), more frequent co-occurrence mutation, and worse efficacy of immunotherapy. This study highlights a new prognostic signature, the BMGPI. BMGPI is an independent predictor of prognosis in PCa patients and is closely associated with the immune microenvironment and the efficacy of immunotherapy.


Assuntos
Neoplasias Ósseas , Aprendizado de Máquina , Células Neoplásicas Circulantes , Neoplasias da Próstata , Humanos , Algoritmos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Neoplasias Ósseas/secundário , Neoplasias Ósseas/genética , Células Neoplásicas Circulantes/patologia , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Mapas de Interação de Proteínas , Microambiente Tumoral
6.
J Cancer Res Clin Oncol ; 150(2): 64, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300330

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the main type of renal cell carcinoma. Cyclin B2 (CCNB2) is a subtype of B-type cyclin that is associated with the prognosis of several cancers. This study aimed to identify the relationship between CCNB2 and progression of ccRCC and construct a novel lncRNAs-related model to predict prognosis of ccRCC patients. METHODS: The data were obtained from public databases. We identified CCNB2 in ccRCC using Kaplan-Meier survival analysis, univariate and multivariate Cox regression, and Gene Ontology analysis. External validation was then performed. The risk model was constructed based on prognostic lncRNAs by the LASSO algorithm and multivariate Cox regression. Receiver operating characteristics (ROC) curves were used to evaluate the model. Consensus clustering analysis was performed to re-stratify the patients. Finally, we analyzed the tumor-immune microenvironment and performed screening of potential drugs. RESULTS: CCNB2 associated with late clinicopathological parameters and poor prognosis in ccRCC and was an independent predictor for disease-free survival. In addition, CCNB2 shared the same expression pattern with known suppressive immune checkpoints. A risk model dependent on the expression of three prognostic CCNB2-related lncRNAs (SNHG17, VPS9D1-AS1, and ZMIZ1-AS1) was constructed. The risk signature was an independent predictor of ccRCC. The area under the ROC (AUC) curve for overall survival at 1-, 3-, 5-, and 8-year was 0.704, 0.702, 0.741, and 0.763. The high-risk group and cluster 2 had stronger immunogenicity and were more sensitive to immunotherapy. CONCLUSION: CCNB2 could be an important biomarker for predicting prognosis in ccRCC patients. Furthermore, we developed a novel lncRNAs-related risk model and identified two CCNB2-related molecular clusters. The risk model performed well in predicting overall survival and immunological microenvironment of ccRCC.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , RNA Longo não Codificante , Humanos , Carcinoma de Células Renais/genética , RNA Longo não Codificante/genética , Ciclina B2/genética , Regulação para Cima , Prognóstico , Neoplasias Renais/genética , Microambiente Tumoral
7.
Front Endocrinol (Lausanne) ; 15: 1358416, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405157

RESUMO

Background: There is still limited research on the association between immune cells and the risk of prostate cancer. Further investigations are warranted to comprehend the intricate associations at play. Methods: We used a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between immune cell phenotypes and prostate cancer. The summary data for immune cell phenotypes was derived from a study cohort, including 3,757 individuals from Sardinia with data on 731 immune cell phenotypes. The summary data for prostate cancer were obtained from the UK Biobank database. Sensitivity analyses were conducted, and the combination of MR-Egger and MR-Presso was used to assess horizontal pleiotropy. Cochran's Q test was employed to evaluate heterogeneity, and the results were subjected to FDR correction. Results: Our study identified two immune cell phenotypes significantly associated with the risk of prostate cancer, namely CD25 on naive-mature B cells (OR = 0.998, 95% CI, 0.997-0.999, P = 2.33E-05, FDR = 0.017) and HLA DR on CD14- CD16- cells (OR = 1.001, 95% CI, 1.000-1.002, P = 8.01E-05, FDR = 0.03). When adjusting FDR to 0.2, we additionally found six immune cell phenotypes influencing the incidence of prostate cancer. These include FSC-A on B cells (OR = 1.002, 95% CI, 1.001-1.002, P = 7.77E-04, FDR = 0.133), HLA DR on plasmacytoid dendritic cells (OR = 1.001, 95% CI, 1.000-1.001, P = 0.001, FDR = 0.133), CD14+ CD16- monocyte % monocytes (OR = 1.002, 95% CI, 1.001-1.003, P = 0.001, FDR = 0.133), and HVEM on effector memory CD4+ T cells (OR = 1.001, 95% CI, 1.000-1.002, P = 0.002, FDR = 0.169), which are positively correlated with the risk of prostate cancer. Conversely, CD25 on IgD+ B cells (OR = 0.998, 95% CI, 0.997-0.999, P = 0.002, FDR = 0.169) and Monocytic Myeloid-Derived Suppressor Cells AC (OR = 0.999, 95% CI, 0.999-1.000, P = 0.002, FDR = 0.17) are negatively correlated with the risk of prostate cancer. Conclusion: This study has revealed causal relationships between immune cell phenotypes and prostate cancer, supplying novel insights that might aid in identifying potential therapeutic targets of prostate cancer.


Assuntos
Análise da Randomização Mendeliana , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/genética , Linfócitos B , Bases de Dados Factuais , Antígenos HLA-DR
8.
Front Endocrinol (Lausanne) ; 15: 1335146, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344665

RESUMO

Introduction: Testosterone replacement therapy (TRT) is a generally accepted method treating for aging-related late-onset hypogonadism (LOH). However, the efficacy and safety of TRT remain controversial. An updated systematic review and meta-analysis aimed to determine the effectiveness and security of TRT treating for LOH. Methods: Randomized controlled trials (RCTs) of TRT for LOH were searched in the databases of Pubmed, Embase, Clinicaltrials.gov and Cochrane from 1990 to 2023 and an updated meta-analysis was conducted. Results: The results of 28 RCTs involving 3461 patients were included and scrutinized in this analysis. Among these, 11 RCTs were of long-term duration (≥12 months), while 18 RCTs were short-term studies (<12 months) comparing TRT with a placebo. TRT modalities comprised injection, oral administration, and transdermal administration. International Index of Erectile Function (IIEF) (Weighted Mean difference (WMD) 3.26; 95%; 95% confidence interval (CI) 1.65-4.88; P<0.0001) was obviously improved in the TRT group. International Prostate Symptom Score (IPSS) (WMD 0.00; 95% CI -0.45-0.45; P=1.0), Prostate Volume (PV) (WMD 0.38; 95% CI -0.64-1.41; P=0.46), Maximum Flow Rate (Qmax) (WMD 1.86; 95% CI -0.98-4.69; P=0.20), Postvoid Residual Urine Volume (PVR) (WMD 3.20; 95% CI -5.87-12.28; P=0.49) and Prostate-Specific Antigen (PSA) (WMD 0.08; 95% CI -0.00-0.17; P=0.06) were not significantly statistical between two groups. Conclusion: This meta-analysis reveals that TRT could improve the IIEF score of hypogonadal men without detriment to the IPSS score, PV, Qmax, PVR and PSA regardless of the administration method or duration of treatment.The meta-analysis was registered at PROSPERO (CRD42023413434).


Assuntos
Disfunção Erétil , Hipogonadismo , Humanos , Masculino , Disfunção Erétil/tratamento farmacológico , Hipogonadismo/tratamento farmacológico , Hipogonadismo/diagnóstico , Próstata , Antígeno Prostático Específico , Testosterona/uso terapêutico , Envelhecimento
9.
Front Endocrinol (Lausanne) ; 15: 1356959, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39391879

RESUMO

Background: Non-obstructive azoospermia (NOA) is a major contributor of male infertility. Herein, we used existing datasets to identify novel biomarkers for the diagnosis and prognosis of NOA, which could have great significance in the field of male infertility. Methods: NOA datasets were obtained from the Gene Expression Omnibus (GEO) database. CIBERSORT was utilized to analyze the distributions of 22 immune cell populations. Hub genes were identified by applying weighted gene co-expression network analysis (WGCNA), machine learning methods, and protein-protein interaction (PPI) network analysis. The expression of hub genes was verified in external datasets and was assessed by receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis (GSEA) was applied to explore the important functions and pathways of hub genes. The mRNA-microRNA (miRNA)-transcription factors (TFs) regulatory network and potential drugs were predicted based on hub genes. Single-cell RNA sequencing data from the testes of patients with NOA were applied for analyzing the distribution of hub genes in single-cell clusters. Furthermore, testis tissue samples were obtained from patients with NOA and obstructive azoospermia (OA) who underwent testicular biopsy. RT-PCR and Western blot were used to validate hub gene expression. Results: Two immune-related oxidative stress hub genes (SHC1 and FGFR1) were identified. Both hub genes were highly expressed in NOA samples compared to control samples. ROC curve analysis showed a remarkable prediction ability (AUCs > 0.8). GSEA revealed that hub genes were predominantly enriched in toll-like receptor and Wnt signaling pathways. A total of 24 TFs, 82 miRNAs, and 111 potential drugs were predicted based on two hub genes. Single-cell RNA sequencing data in NOA patients indicated that SHC1 and FGFR1 were highly expressed in endothelial cells and Leydig cells, respectively. RT-PCR and Western blot results showed that mRNA and protein levels of both hub genes were significantly upregulated in NOA testis tissue samples, which agree with the findings from analysis of the microarray data. Conclusion: It appears that SHC1 and FGFR1 could be significant immune-related oxidative stress biomarkers for detecting and managing patients with NOA. Our findings provide a novel viewpoint for illustrating potential pathogenesis in men suffering from infertility.


Assuntos
Azoospermia , Biomarcadores , Estresse Oxidativo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src , Humanos , Masculino , Estresse Oxidativo/genética , Azoospermia/genética , Azoospermia/metabolismo , Azoospermia/patologia , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/genética , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Biomarcadores/metabolismo , Biomarcadores/análise , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Testículo/metabolismo , Testículo/patologia , Perfilação da Expressão Gênica , Adulto
10.
J Cancer Res Clin Oncol ; 149(17): 15805-15818, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37668798

RESUMO

BACKGROUND: Disulfidptosis, as a new mode of programmed cell death, is closely associated with tumorigenesis. Meanwhile, M2 tumor-associated macrophage (TAM) plays an important role in tumor progression. Here, we propose to combine these two perspectives to detect novel disulfidptosis and M2 TAM-related biomarkers in bladder cancer (BCa) to identify various tumor subtypes, construct prognostic features, reveal immune and somatic mutational landscapes, and screen for drugs in BCa. METHODS: We used weighted gene co-expression network analysis (WGCNA) to mine M2 TAM-related genes. Consensus unsupervised clustering was performed to identify potential tumor subtypes. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were utilized to build the risk model. We then explored the immune cell, immune function, immune checkpoint expression patterns and somatic mutational landscape in clusters and risk groups. In addition, we performed sensitivity analysis for anti-cancer drugs. RESULTS: We identified 3057 M2 TAM-related genes and intersected them with disulfidptosis-related genes to obtain 95 disulfidptosis and M2 TAM-related genes (DMRGs). In terms of tumor subtypes, two molecular clusters were identified. Cluster 1 showed stronger immunogenicity and higher tumor mutational burden (TMB). We also predicted 50 drugs with high sensitivity in cluster 1. On the basis of risk grouping, the high-risk group had poor overall survival in the training, test, and validation groups. Ten screened anti-cancer drugs were more sensitive in the high-risk group. A nomogram predicting survival of BCa patients was also established. CONCLUSION: By combining two hotspot perspectives, disulfidptosis and M2 TAM, we provide a valuable risk score signature for establishing individualized treatment regimens and drug choices. The risk score may serve as an independent risk factor for BCa patients.


Assuntos
Antineoplásicos , Neoplasias da Bexiga Urinária , Humanos , Macrófagos Associados a Tumor , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Carcinogênese , Apoptose
11.
Sex Med ; 11(3): qfad036, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37502219

RESUMO

Background: The relationship between erectile dysfunction (ED) and physical activity has been established in several previous studies, but there is little information on the specific forms of activity that affect ED. Aim: The objective of this study was to evaluate the relationship of 4 exercise categories and 2 activity intensities with ED in US men. Methods: We used data sets from the National Health and Nutrition Examination Survey, 2001-2004. We used odds ratios (ORs) and multivariate logistic regression models to investigate the relationship between physical activity and ED. We also conducted subgroup analyses by age and controlled for potential confounder variables using propensity score matching analyses. Outcomes: The primary outcome was ED as assessed through self-reporting. Results: An overall 4094 adult men were included in the study. Adjusted multivariate regression models indicated that men who participated in monthly muscle-strengthening activities (OR = 0.75, P = .031), leisure activities (OR = 0.76, P = .024), or vigorous activities (OR = 0.64, P = .001) had a lower risk of ED. The subgroup analysis showed that among those ≥40 years old, muscle-strengthening activity (OR = 0.67, P = .005), leisure activity (OR = 0.72, P = .006), and vigorous activity (OR = 0.50, P < .001) were negatively associated with ED. After adjustment of propensity score matching, leisure activity and vigorous activity were also associated with a lower risk of ED, and muscle-strengthening activity was not significantly associated with ED. Clinical Implications: Our findings could provide guidance to clinicians in helping patients with ED develop exercise programs. Strengths and Limitations: We explored the relationship of 4 types and 2 intensities of exercise with ED, using a large sample size and sampling weights to produce representative data. However, this is only a cross-sectional study. Conclusion: Active monthly participation in leisure and vigorous activity is associated with the maintenance of erectile function, while the relevance of muscle-strengthening activities needs further study.

12.
Front Endocrinol (Lausanne) ; 14: 1225033, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027160

RESUMO

Background: Studies using novel antiandrogens (NAA) in patients with metastatic castration-resistant prostate cancer (mCRPC) have shown overall survival benefit. As patients develop resistance to NAA therapy, the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib in combination with NAA may become a promising therapy. However the overall benefit of olaparib monotherapy or combination therapy still needs to be evaluated. Therefore, we performed a network meta-analysis to assess the efficacy and toxicity between olaparib, olaparib combined with abiraterone and NAA. Methods: We searched PubMed, EMBASE, the Cochrane Library and American Society of Clinical Oncology (ASCO) University Meeting abstracts for randomized controlled trials reporting olaparib and NAA from 2010 up to March, 2023. Network meta-analysis using Stata 16.0 and R 4.4.2, hazard ratios (HR) with 95% confidence intervals (CI) were used to assess the results. Results: Four trials reported olaparib, olaparib plus abiraterone and apalutamide plus abiraterone. radiographic progression-free survival (rPFS) was significantly lower in patients on apalutamide plus abiraterone compared to olaparib (HR, 1.43; 95% CI, 1.06-1.93). rPFS was similar for olaparib plus abiraterone and olaparib (HR, 1.35; 95% CI, 0.99-1.84); likewise, olaparib plus abiraterone and apalutamide plus abiraterone were similar (HR, 1.06; 95% CI, 0.83-1.35). In addition, there was no significant difference between the three interventions for OS. But olaparib has the highest probability of being a preferred treatment for improving rPFS and OS. Conclusion: rPFS was in favor of olaparib compared with apalutamide plus abiraterone. But there were no difference between olaparib plus abiraterone and either olaparib or apalutamide plus abiraterone. Apalutamide plus abiraterone might be the most preferred intervention in cases where AEs are involved. Systematic review registration: https://inplasy.com, identifier INPLASY2023100072.


Assuntos
Antineoplásicos , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Antagonistas de Androgênios , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antineoplásicos/uso terapêutico
13.
Front Endocrinol (Lausanne) ; 14: 1148117, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37033267

RESUMO

Background: The prostate, as an endocrine and reproductive organ, undergoes complex hormonal and metabolic changes. Recent studies have shown a potential relationship between metabolic syndrome and the progression and recurrence of prostate cancer (PCa). This study aimed to construct a metabolic syndrome-related prognostic index (MSRPI) to predict biochemical recurrence-free survival (BFS) in patients with PCa and to identify cold and hot tumors to improve individualized treatment for patients with PCa. Methods: The Cancer Genome Atlas database provided training and test data, and the Gene Expression Omnibus database provided validation data. We extracted prognostic differentially expressed metabolic syndrome-related genes (DEMSRGs) related to BFS using univariate Cox analysis and identified potential tumor subtypes by consensus clustering. The least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression were used to construct the MSRPI. We further validated the predictive power of the MSRPI using KaplanMeier survival analysis and receiver operating characteristic (ROC) curves, both internally and externally. Drug sensitivity was predicted using the half-maximal inhibitory concentration (IC50). Finally, we explored the landscape of somatic mutations in the risk groups. Results: Forty-six prognostic DEMSRGs and two metabolic syndrome-associated molecular clusters were identified. Cluster 2 was more immunogenic. Seven metabolic syndrome-related genes (CSF3R, TMEM132A, STAB1, VIM, DUOXA1, PILRB, and SLC2A4) were used to construct risk equations. The high-risk index was significantly associated with a poor BFS, which was also validated in the validation cohort. The area under the ROC curve (AUC) for BFS at 1-, 3-, and 5- year in the entire cohort was 0.819, 0.785, and 0.772, respectively, demonstrating the excellent predictive power of the MSRPI. Additionally, the MSRPI was found to be an independent prognostic factor for BFS in PCa. More importantly, MSRPI helped differentiate between cold and hot tumors. Hot tumors were associated with the high-risk group. Multiple drugs demonstrated significantly lower IC50 values in the high-risk group, offering the prospect of precision therapy for patients with PCa. Conclusion: The MSRPI developed in this study was able to predict biochemical recurrence in patients with PCa and identify cold and hot tumors. MSRPI has the potential to improve personalized precision treatment.


Assuntos
Síndrome Metabólica , Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Próstata , Algoritmos
14.
Front Immunol ; 14: 1172724, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37426635

RESUMO

Background: COVID-19, a serious respiratory disease that has the potential to affect numerous organs, is a serious threat to the health of people around the world. The objective of this article is to investigate the potential biological targets and mechanisms by which SARS-CoV-2 affects benign prostatic hyperplasia (BPH) and related symptoms. Methods: We downloaded the COVID-19 datasets (GSE157103 and GSE166253) and the BPH datasets (GSE7307 and GSE132714) from the Gene Expression Omnibus (GEO) database. In GSE157103 and GSE7307, differentially expressed genes (DEGs) were found using the "Limma" package, and the intersection was utilized to obtain common DEGs. Further analyses followed, including those using Protein-Protein Interaction (PPI), Gene Ontology (GO) function enrichment analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Potential hub genes were screened using three machine learning methods, and they were later verified using GSE132714 and GSE166253. The CIBERSORT analysis and the identification of transcription factors, miRNAs, and drugs as candidates were among the subsequent analyses. Results: We identified 97 common DEGs from GSE157103 and GSE7307. According to the GO and KEGG analyses, the primary gene enrichment pathways were immune-related pathways. Machine learning methods were used to identify five hub genes (BIRC5, DNAJC4, DTL, LILRB2, and NDC80). They had good diagnostic properties in the training sets and were validated in the validation sets. According to CIBERSORT analysis, hub genes were closely related to CD4 memory activated of T cells, T cells regulatory and NK cells activated. The top 10 drug candidates (lucanthone, phytoestrogens, etoposide, dasatinib, piroxicam, pyrvinium, rapamycin, niclosamide, genistein, and testosterone) will also be evaluated by the P value, which is expected to be helpful for the treatment of COVID-19-infected patients with BPH. Conclusion: Our findings reveal common signaling pathways, possible biological targets, and promising small molecule drugs for BPH and COVID-19. This is crucial to understand the potential common pathogenic and susceptibility pathways between them.


Assuntos
COVID-19 , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/genética , COVID-19/genética , SARS-CoV-2 , Genes cdc , Algoritmos
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