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Cussenot O, Taille Y, Portal JJ, Cancel-Tassin G, Rouprêt M, de la Taille A, Ploussard G, Mathieu R, Vicaut E. Eliciting the Impact of Metformin and Statins on Prostate Cancer Outcomes from a Real-life National Database Analysis. Eur Urol Oncol 2025:S2588-9311(25)00121-X. [PMID: 40348654 DOI: 10.1016/j.euo.2025.04.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Accepted: 04/24/2025] [Indexed: 05/14/2025]
Abstract
Several large analyses have revealed contradictory results regarding the association between prostate cancer (PC) survival and the use of statins prescribed for prevention of dyslipidaemia or atherosclerosis complications, or of metformin prescribed for type 2 diabetes (T2D). Using data collected between 2006 and 2018 in French national health databases for 521 052 men with PC and 1 827 345 men without PC, we evaluated current evidence regarding overall survival for men with PC according to statin and/or metformin use. The highest mortality was observed in PC patients exposed to both statins and metformin (hazard ratio [HR] 2.29, 95% confidence interval [CI] 2.25-2.33). However, for patients whose first PC treatment was androgen deprivation therapy, a protective effect was observed for statin alone exposure (HR 0.91, 95% CI 0.88-0.93) and combined statin and metformin exposure (HR 0.86, 95% CI 0.85-0.87), whereas men with metformin exposure alone had higher mortality (HR 1.07, 95% CI 1.03-1.11) in comparison to non-users. This protective effect of statins was not observed for PC patients treated with radical prostatectomy. The result was confirmed using causal analysis in a Bayesian network, followed by semantic elicitation using generative artificial intelligence that compiles web-based human knowledge and dedicated literature.
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Affiliation(s)
- Olivier Cussenot
- Universitätsklinik für Urologie, Medical University Vienna, Vienna, Austria; Centre de Recherche sur les Pathologies Prostatiques, Paris, France.
| | - Yoann Taille
- Clinical Reasearch Unit, Hôpitaux Saint Louis-Lariboisière-Fernand Widal, AP-HP, University Paris Cité, Paris, France
| | - Jean-Jacques Portal
- Clinical Reasearch Unit, Hôpitaux Saint Louis-Lariboisière-Fernand Widal, AP-HP, University Paris Cité, Paris, France
| | - Géraldine Cancel-Tassin
- Centre de Recherche sur les Pathologies Prostatiques, Paris, France; GRC No. 5 Predictive Onco-Urology, Hôpital Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France
| | - Morgan Rouprêt
- Centre de Recherche sur les Pathologies Prostatiques, Paris, France; GRC No. 5 Predictive Onco-Urology, Hôpital Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France
| | - Alexandre de la Taille
- Department of Urology, Hôpitaux Universitaires Henri Mondor, AP-HP, University of Creteil, Créteil, France
| | | | | | - Eric Vicaut
- Clinical Reasearch Unit, Hôpitaux Saint Louis-Lariboisière-Fernand Widal, AP-HP, University Paris Cité, Paris, France
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2
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Huo X, Wang Z, Huang N, Zhang J. Glycemic control and prostate antigen levels in individuals with diabetes based on NHANES data. Sci Rep 2025; 15:15828. [PMID: 40328819 PMCID: PMC12055993 DOI: 10.1038/s41598-025-00853-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 04/30/2025] [Indexed: 05/08/2025] Open
Abstract
The relationship between diabetes and prostate-specific antigen (PSA) levels is complex, with potential implications for prostate cancer screening. This study examined the association between glycemic control and total PSA (tPSA) levels in patients with diabetes. We analyzed data from the 2001-2010 NHANES to assess the relationship between glycated hemoglobin (HbA1c) and tPSA in adults with diabetes, categorizing HbA1c as < 7% (good glycemic control) or ≥ 7% (poor glycemic control). Multivariable regression models were used, adjusting for key demographic, clinical, and lifestyle factors, including age, race/ethnicity, marital status, body mass index (BMI), smoking status, alcohol use, hypertension, coronary artery disease (CAD), and insulin use. Adjustments for multiple comparisons were considered using the Bonferroni correction, and missing data were handled using multiple imputation. Participants with poor glycemic control were younger, less likely to be married or partnered, and had higher rates of insulin use but lower hypertension incidence than those with good glycemic control (P < 0.05). The median tPSA level was greater in the good control group (1.10 ng/mL vs. 0.90 ng/mL; P = 0.0014). Multivariate analysis revealed no overall association between HbA1c and tPSA (β = -0.022, P = 0.917). However, significant inverse associations were observed across subgroups, including those aged ≤ 59 years (β = -0.71, P = 0.033), married individuals (β = -0.55, P < 0.001), participants without CAD (β = -0.49, P = 0.015), and insulin users (β = -0.80, P = 0.031). Although no significant overall association was found between glycemic control and tPSA levels, subgroup analyses revealed an inverse relationship between HbA1c and tPSA in younger individuals (≤ 59 years), insulin users, and those without CAD. These findings suggest that glycemic control may have subgroup-specific effects on prostate health in individuals with diabetes.
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Affiliation(s)
- Xiao Huo
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhi Wang
- Huazhong University of Science and Technology, Wuhan, China
| | - Nan Huang
- Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jie Zhang
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Pagoni M, Zogopoulos VL, Kontogiannis S, Tsolakou A, Zoumpourlis V, Tsangaris GT, Fokaefs E, Michalopoulos I, Tsatsakis AM, Drakoulis N. Integrated Pharmacogenetic Signature for the Prediction of Prostatic Neoplasms in Men With Metabolic Disorders. Cancer Genomics Proteomics 2025; 22:285-305. [PMID: 39993800 PMCID: PMC11880924 DOI: 10.21873/cgp.20502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/14/2025] [Accepted: 01/16/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND/AIM Oncogenic processes are delineated by metabolic dysregulation. Drug likeness is pharmacokinetically tested through the CYP450 enzymatic system, whose genetic aberrations under epigenetic stress could shift male organisms into prostate cancer pathways. Our objective was to predict the susceptibility to prostate neoplasia, focused on benign prostatic hyperplasia (BPH) and prostate cancer (PCa), based on the pharmacoepigenetic and the metabolic profile of Caucasians. MATERIALS AND METHODS Two independent cohorts of 47,389 individuals in total were assessed to find risk associations of CYP450 genes with prostatic neoplasia. The metabolic profile of the first cohort was statistically evaluated and frequencies of absorption-distribution-metabolism-excretion-toxicity (ADMET) properties were calculated. Prediction of miRNA pharmacoepigenetic targeting was performed. RESULTS We found that prostate cancer and benign prostatic hyperplasia patients of the first cohort shared common cardiometabolic trends. Drug classes C08CA, C09AA, C09CA, C10AA, C10AX of the cardiovascular, and G04CA, G04CB of the genitourinary systems, were associated with increased prostate cancer risk, while C03CA and N06AB of the cardiovascular and nervous systems were associated with low-risk for PCa. CYP3A4*1B was the most related pharmacogenetic polymorphism associated with prostate cancer susceptibility. miRNA-200c-3p and miRNA-27b-3p seem to be associated with CYP3A4 targeting and prostate cancer predisposition. Metabolomic analysis indicated that 11β-OHT, 2β-OHT, 15β-OHT, 2α-OHT and 6β-OHT had a high risk, and 16α-OHT, and 16β-OHT had an intermediate disease-risk. CONCLUSION These findings constitute a novel integrated signature for prostate cancer susceptibility. Further studies are required to assess their predictive value more fully.
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Affiliation(s)
- Maria Pagoni
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece;
| | - Vasileios L Zogopoulos
- Centre of Systems Biology, Biomedical Research Foundation, Academy of Athens, Athens, Greece
| | | | - Annia Tsolakou
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece
| | | | - George Th Tsangaris
- Proteomics Research Unit, Biomedical Research Foundation, Academy of Athens, Athens, Greece;
| | | | - Ioannis Michalopoulos
- Centre of Systems Biology, Biomedical Research Foundation, Academy of Athens, Athens, Greece
| | - Aristidis M Tsatsakis
- Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Nikolaos Drakoulis
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece
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4
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Khan A, Sarkar E, Chandra A, Raza ST, Mahdi AA, Sankhwar SN, Agarwal P, Gupta A. Serum Insulin, Insulin-Like Growth Factor-1, Testosterone and Lipid Profile Levels in Benign Prostatic Hyperplasia and Prostate Cancer at Diagnosis. Cureus 2024; 16:e75342. [PMID: 39781138 PMCID: PMC11707001 DOI: 10.7759/cureus.75342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/08/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND AND OBJECTIVES Prostate cancer is the second most frequently diagnosed cancer in men aged 65 years and older globally. The association of prostate cancer with deranged lipid profile and insulin levels is inconsistent and not well understood. This study aimed to analyze the serum levels of lipids, insulin, insulin-like growth factor-1 (IGF-1) and testosterone and to identify their association with the risk of benign prostatic hyperplasia, prostate cancer and its grading. MATERIALS AND METHODS This case-control study includes 150 individuals. Cases were 50 newly diagnosed benign prostatic hyperplasia (BPH) and 50 histologically confirmed prostate adenocarcinoma patients. Fifty age-matched disease-free controls were included. Results were analyzed using descriptive statistics and summarized as mean ± standard deviation. ANOVA was used to determine statistically significant differences between two or more categorical groups. Chi-square was used to determine the association between variables of interest. RESULTS Data showed that serum insulin and IGF-1 were significantly elevated in prostate cancer and BPH, the highest being in the prostate cancer group, and had a significant positive association with prostate cancer Gleason score and grade. However, lipid profile had non-significant association with prostate cancer Gleason score and grade. CONCLUSION This study confirms the association of insulin and IGF-1 with BPH and prostate cancer Gleason score and grade.
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Affiliation(s)
- Afreen Khan
- Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, IND
| | - Esha Sarkar
- Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, IND
| | - Anu Chandra
- Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, IND
| | - Syed Tasleem Raza
- Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, IND
| | - Abbas A Mahdi
- Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, IND
| | - S N Sankhwar
- Urology, King George's Medical University, Lucknow, IND
| | - Preeti Agarwal
- Pathology, King George's Medical University, Lucknow, IND
| | - Avneet Gupta
- Urology, Precision Urology Hospital, Lucknow, IND
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5
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Li J, Li ZP, Xu SS, Wang W. Unraveling the biological link between diabetes mellitus and prostate cancer: Insights and implications. World J Diabetes 2024; 15:1367-1373. [PMID: 38983816 PMCID: PMC11229951 DOI: 10.4239/wjd.v15.i6.1367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 03/15/2024] [Accepted: 04/18/2024] [Indexed: 06/11/2024] Open
Abstract
This article is a comprehensive study based on research on the connection between diabetes mellitus (DM) and prostate cancer (PCa). It investigates the potential role of DM as an independent risk factor for PCa, delving into the biological links, including insulin resistance and hormonal changes. The paper critically analyzes previous studies that have shown varying results and introduces mendelian randomization as a method for establishing causality. It emphasizes the importance of early DM screening and lifestyle modifications in preventing PCa, and proposes future research directions for further under-standing the DM - PCa relationship.
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Affiliation(s)
- Jian Li
- Department of Interventional Oncology, Municipal Hospital Affiliated to Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Zhi-Peng Li
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Si-Si Xu
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Wei Wang
- Department of Interventional Oncology, Municipal Hospital Affiliated to Taizhou University, Taizhou 318000, Zhejiang Province, China
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6
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Bisceglia I, Canale ML, Silvestris N, Gallucci G, Camerini A, Inno A, Camilli M, Turazza FM, Russo G, Paccone A, Mistrulli R, De Luca L, Di Fusco SA, Tarantini L, Lucà F, Oliva S, Moreo A, Maurea N, Quagliariello V, Ricciardi GR, Lestuzzi C, Fiscella D, Parrini I, Racanelli V, Russo A, Incorvaia L, Calabrò F, Curigliano G, Cinieri S, Gulizia MM, Gabrielli D, Oliva F, Colivicchi F. Cancer survivorship at heart: a multidisciplinary cardio-oncology roadmap for healthcare professionals. Front Cardiovasc Med 2023; 10:1223660. [PMID: 37786510 PMCID: PMC10541962 DOI: 10.3389/fcvm.2023.1223660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 08/24/2023] [Indexed: 10/04/2023] Open
Abstract
In cancer, a patient is considered a survivor from the time of initial diagnosis until the end of life. With improvements in early diagnosis and treatment, the number of cancer survivors (CS) has grown considerably and includes: (1) Patients cured and free from cancer who may be at risk of late-onset cancer therapy-related cardiovascular toxicity (CTR-CVT); (2) Patients with long-term control of not-curable cancers in whom CTR-CVT may need to be addressed. This paper highlights the importance of the cancer care continuum, of a patient-centered approach and of a prevention-oriented policy. The ultimate goal is a personalized care of CS, achievable only through a multidisciplinary-guided survivorship care plan, one that replaces the fragmented management of current healthcare systems. Collaboration between oncologists and cardiologists is the pillar of a framework in which primary care providers and other specialists must be engaged and in which familial, social and environmental factors are also taken into account.
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Affiliation(s)
- Irma Bisceglia
- Integrated Cardiology Services, Cardio-Thoracic-Vascular Department, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Maria Laura Canale
- Division of Cardiology, Ospedale Versilia, Azienda Usl Toscana Nord Ovest, Lido di Camaiore, Italy
| | - Nicola Silvestris
- Unit of Medical Oncology, Department of Human Pathology in Adulthood and Childhood Gaetano Barresi, University of Messina, Messina, Italy
| | - Giuseppina Gallucci
- Cardio-oncology Unit, Department of OncoHaematology, IRCCS Referral Cancer Center of Basilicata, Rionero in Vulture (PZ), Italy
| | - Andrea Camerini
- Department of Medical Oncology, Ospedale Versilia, Azienda Usl Toscana Nord Ovest, Lido di Camaiore, Italy
| | - Alessandro Inno
- Department of Oncology, Sacro Cuore Don Calabria Hospital (IRCCS), Negrar, Italy
| | - Massimiliano Camilli
- Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart and Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Fabio Maria Turazza
- Cardiology Department, National Cancer Institute Foundation (IRCCS), Milan, Italy
| | - Giulia Russo
- SC Patologie Cardiovascolari, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Trieste, Italy
| | - Andrea Paccone
- Department of Cardiology, G. Pascale National Cancer Institute Foundation (IRCCS), Naples, Italy
| | - Raffaella Mistrulli
- Cardiology Unit, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Lazio, Italy
| | - Leonardo De Luca
- Division of Cardiology, San Camillo-Forlanini Hospital, Rome, Italy
| | | | - Luigi Tarantini
- Divisione di Cardiologia, Arcispedale S. Maria Nuova, Azienda Unità Sanitaria Locale-IRCCS di Reggio-Emilia, Reggio Emilia, Italy
| | - Fabiana Lucà
- Cardiologia Interventistica, Utic, Grande Ospedale Metropolitano, Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio Calabria, Italy
| | - Stefano Oliva
- UOSD Cardiologia di Interesse Oncologico, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - Antonella Moreo
- Cardio Center De Gasperis, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Nicola Maurea
- Department of Cardiology, G. Pascale National Cancer Institute Foundation (IRCCS), Naples, Italy
| | - Vincenzo Quagliariello
- Department of Cardiology, G. Pascale National Cancer Institute Foundation (IRCCS), Naples, Italy
| | | | | | - Damiana Fiscella
- U.O.C. Cardiologia, Ospedale Garibaldi-Nesima, Azienda di Rilievo Nazionale e Alta Specializzazione “Garibaldi”, Catania, Italy
| | - Iris Parrini
- Department of Cardiology, Hospital Mauritian Turin, Turin, Italy
| | - Vito Racanelli
- Department of Interdisciplinary Medicine, School of Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Antonio Russo
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, Palermo University Hospital, Palermo, Italy
| | - Lorena Incorvaia
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, Palermo University Hospital, Palermo, Italy
| | - Fabio Calabrò
- Department of Oncology and Specialized Medicine, San Camillo-Forlanini Hospital, Rome, Italy
| | - Giuseppe Curigliano
- Department of Oncology and Hemato-Oncology, University of Milan; Division of Early Drug Development, Istituto Europeo di Oncologia, IRCCS, Milan, Italy
| | - Saverio Cinieri
- Medical Oncology Division and Breast Unit, Senatore Antonio Perrino Hospital, ASL Brindisi, Brindisi, Italy
| | - Michele Massimo Gulizia
- U.O.C. Cardiologia, Ospedale Garibaldi-Nesima, Azienda di Rilievo Nazionale e Alta Specializzazione “Garibaldi”, Catania, Italy
| | - Domenico Gabrielli
- Division of Cardiology, San Camillo-Forlanini Hospital, Rome, Italy
- Fondazione per il Tuo cuore- Heart Care Foundation, Firenze, Italy
| | - Fabrizio Oliva
- Cardiologia 1- Emodinamica, Dipartimento Cardiotoracovascolare “A. De Gasperis”, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Furio Colivicchi
- Clinical and Rehabilitation Cardiology Unit, San Filippo Neri Hospital, ASL Roma 1, Rome, Italy
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7
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Ledda C, Bracci M, Spadafora A, Motta G, Smecca G, Catelan D, Rapisarda V. Unmasking the Hidden Danger: A Decade-Long Systematic Review of Case-Control Studies on Single Occupational Risks and Prostate Cancer. Life (Basel) 2023; 13:1820. [PMID: 37763224 PMCID: PMC10532927 DOI: 10.3390/life13091820] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/21/2023] [Accepted: 08/26/2023] [Indexed: 09/29/2023] Open
Abstract
The present systematic review addresses the influence of occupational exposures on prostate cancer risk. Eleven studies were analyzed for a range of occupational exposures, including but not limited to firefighting, physical activity, night shift work, chemical exposure, and solar ultraviolet radiation. The results of the review reveal that firefighters exposed to harmful substances, individuals engaged in physically strenuous work, and workers with chronic night shift routines showed an increased likelihood of developing prostate cancer. Moreover, the review identified an increased risk associated with exposure to certain chemicals, including alkylphenolic compounds and benzene-related substances. The evidence underscores the importance of considering the cumulative effect of multiple risk factors in a comprehensive risk assessment. However, the conclusions indicate the necessity for further research to deepen these relationships and develop more effective strategies for the prevention of prostate cancer.
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Affiliation(s)
- Caterina Ledda
- Occupational Medicine, Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy;
| | - Massimo Bracci
- Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60121 Ancona, Italy;
| | - Alba Spadafora
- Occupational Health and Safety Unit, Provincial Health Agency of Siracusa, 96100 Siracusa, Italy;
| | - Giuseppe Motta
- Occupational Medicine Unit, “Garibaldi” Hospital of Catania, 95123 Catania, Italy;
| | - Giuseppe Smecca
- Prevention and Protection Unit, Provincial Health Agency of Ragusa, 97100 Ragusa, Italy;
| | - Dolores Catelan
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35131 Padova, Italy;
| | - Venerando Rapisarda
- Occupational Medicine, Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy;
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8
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Bellei E, Caramaschi S, Giannico GA, Monari E, Martorana E, Reggiani Bonetti L, Bergamini S. Research of Prostate Cancer Urinary Diagnostic Biomarkers by Proteomics: The Noteworthy Influence of Inflammation. Diagnostics (Basel) 2023; 13:diagnostics13071318. [PMID: 37046536 PMCID: PMC10093134 DOI: 10.3390/diagnostics13071318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 03/28/2023] [Accepted: 03/31/2023] [Indexed: 04/05/2023] Open
Abstract
Nowadays, in the case of suspected prostate cancer (PCa), tissue needle biopsy remains the benchmark for diagnosis despite its invasiveness and poor tolerability, as serum prostate-specific antigen (PSA) is limited by low specificity. The aim of this proteomic study was to identify new diagnostic biomarkers in urine, an easily and non-invasively available sample, able to selectively discriminate cancer from benign prostatic hyperplasia (BPH), evaluating whether the presence of inflammation may be a confounding parameter. The analysis was performed by two-dimensional gel electrophoresis (2-DE), mass spectrometry (LC-MS/MS) and Enzyme-Linked Immunosorbent Assay (ELISA) on urine samples from PCa and BPH patients, divided into subgroups based on the presence or absence of inflammation. Significant quantitative and qualitative differences were found in the urinary proteomic profile of PCa and BPH groups. Of the nine differentially expressed proteins, only five can properly be considered potential biomarkers of PCa able to discriminate the two diseases, as they were not affected by the inflammatory process. Therefore, the proteomic research of novel and reliable urinary biomarkers of PCa should be conducted considering the presence of inflammation as a realistic interfering element, as it could hinder the detection of important protein targets.
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Affiliation(s)
- Elisa Bellei
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance, Proteomic Lab, University of Modena and Reggio Emilia, 41124 Modena, Italy
| | - Stefania Caramaschi
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, AOU Policlinico di Modena, 41124 Modena, Italy
| | - Giovanna A. Giannico
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Emanuela Monari
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance, Proteomic Lab, University of Modena and Reggio Emilia, 41124 Modena, Italy
| | - Eugenio Martorana
- Division of Urology, New Civilian Hospital of Sassuolo, 41049 Modena, Italy
| | - Luca Reggiani Bonetti
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, AOU Policlinico di Modena, 41124 Modena, Italy
| | - Stefania Bergamini
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance, Proteomic Lab, University of Modena and Reggio Emilia, 41124 Modena, Italy
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9
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Wanjari UR, Mukherjee AG, Gopalakrishnan AV, Murali R, Dey A, Vellingiri B, Ganesan R. Role of Metabolism and Metabolic Pathways in Prostate Cancer. Metabolites 2023; 13:183. [PMID: 36837801 PMCID: PMC9962346 DOI: 10.3390/metabo13020183] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 01/21/2023] [Accepted: 01/21/2023] [Indexed: 01/27/2023] Open
Abstract
Prostate cancer (PCa) is the common cause of death in men. The pathophysiological factors contributing to PCa are not well known. PCa cells gain a protective mechanism via abnormal lipid signaling and metabolism. PCa cells modify their metabolism in response to an excessive intake of nutrients to facilitate advancement. Metabolic syndrome (MetS) is inextricably linked to the carcinogenic progression of PCa, which heightens the severity of the disease. It is hypothesized that changes in the metabolism of the mitochondria contribute to the onset of PCa. The studies of particular alterations in the progress of PCa are best accomplished by examining the metabolome of prostate tissue. Due to the inconsistent findings written initially, additional epidemiological research is required to identify whether or not MetS is an aspect of PCa. There is a correlation between several risk factors and the progression of PCa, one of which is MetS. The metabolic symbiosis between PCa cells and the tumor milieu and how this type of crosstalk may aid in the development of PCa is portrayed in this work. This review focuses on in-depth analysis and evaluation of the metabolic changes that occur within PCa, and also aims to assess the effect of metabolic abnormalities on the aggressiveness status and metabolism of PCa.
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Affiliation(s)
- Uddesh Ramesh Wanjari
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, India
| | - Anirban Goutam Mukherjee
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, India
| | - Abilash Valsala Gopalakrishnan
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, India
| | - Reshma Murali
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, India
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, Kolkata 700073, India
| | - Balachandar Vellingiri
- Stem Cell and Regenerative Medicine/Translational Research, Department of Zoology, School of Basic Sciences, Central University of Punjab (CUPB), Bathinda 151401, India
| | - Raja Ganesan
- Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
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10
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Liu Z, Zhu X, He J, Lu J. Metabolic syndrome and its components predict the biochemical recurrence and adverse pathological features of patients following radical prostatectomy: a propensity score matching study. BMC Cancer 2023; 23:50. [PMID: 36641426 PMCID: PMC9840841 DOI: 10.1186/s12885-023-10507-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 01/02/2023] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND To investigate the predictive value of metabolic syndrome (MetS) and its components in biochemical recurrence (BCR) and adverse pathological features of patients with prostate cancer (PCa) after radical prostatectomy (RP). METHODS A total of 525 PCa patients who underwent RP between 2010 and 2019 at Peking University Third Hospital were analyzed retrospectively. The Kaplan-Meier method was performed to assess BCR-free survival (BCRFS). Univariate and multivariate Cox regression models and multivariate logistic regression models were conducted to identify the predictive factors of BCRFS and adverse pathological features respectively before and after propensity score matching (PSM). RESULTS Enrolled patients were allocated into MetS group (n = 136) and non-MetS group (n = 389) according to the presence or absence of MetS, and 127 new matched pairs were identified to balance the baseline characteristics after 1:1 PSM. In propensity matched patients, the Kaplan-Meier analysis revealed that MetS (P = 0.020), hyperglycemia (P = 0.015) and hypertriglyceridemia (P = 0.001) were significantly associated with worse BCRFS; the results of multivariate Cox analyses showed that hyperglycemia (P = 0.040), hypertriglyceridemia (P = 0.017), percentage of positive biopsy cores (P = 0.041) and prostate specific antigen (P = 0.019) were identified as independent prognostic factors for BCRFS. In addition, hypertriglyceridemia was independently associated with non-organ confined disease (NOCD) (P = 0.010), extra-capsular extension (ECE) (P = 0.010) and upgrading (P = 0.017) in the multivariate logistic analyses. CONCLUSIONS Hyperglycemia and hypertriglyceridemia are the two effective MetS components both identified as independent risk factors for worse BCRFS after RP, while hypertriglyceridemia was independently associated with NOCD, ECE and upgrading as well.
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Affiliation(s)
- Zenan Liu
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Xuehua Zhu
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Jide He
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Jian Lu
- Department of Urology, Peking University Third Hospital, Beijing, China.
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Wu H, Huang D, Zhou H, Sima X, Wu Z, Sun Y, Wang L, Ruan Y, Wu Q, Wu F, She T, Chu Y, Huang Q, Ning Z, Zhang H. Metformin: A promising drug for human cancers. Oncol Lett 2022; 24:204. [PMID: 35720480 PMCID: PMC9178677 DOI: 10.3892/ol.2022.13325] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 04/12/2022] [Indexed: 12/12/2022] Open
Abstract
Small-molecule chemical drugs are of great significance for tumor-targeted and individualized therapies. However, the development of new small-molecule drugs, from basic experimental research and clinical trials to final application in clinical practice, is a long process that has a high cost. It takes at least 5 years for most drugs to be developed in the laboratory to prove their effectiveness and safety. Compared with the development of new drugs, repurposing traditional non-tumor drugs can be a shortcut. Metformin is a good model for a new use of an old drug. In recent years, the antitumor efficacy of metformin has attracted much attention. Epidemiological data and in vivo, and in vitro experiments have shown that metformin can reduce the incidence of cancer in patients with diabetes and has a strong antagonistic effect on metabolism-related tumors. Recent studies have shown that metformin can induce autophagy in esophageal cancer cells, mainly by inhibiting inflammatory signaling pathways. In recent years, studies have shown that the antitumor functions and mechanisms of metformin are multifaceted. The present study aims to review the application of metformin in tumor prevention and treatment.
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Affiliation(s)
- Hongnian Wu
- Department of Human Anatomy, Basic Medicine School, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China
| | - Dan Huang
- Department of Burn and Plastic Surgery, Enshi State Central Hospital, Enshi, Hubei 445099, P.R. China
| | - Hong Zhou
- Department of Human Anatomy, Basic Medicine School, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China
| | - Xueqin Sima
- Department of Histology and Embryology, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China
| | - Zhe Wu
- Department of Histology and Embryology, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China
| | - Yanling Sun
- Department of Histology and Embryology, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China
| | - Long Wang
- Department of Microbiology, Basic Medicine School, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China
| | - Ying Ruan
- Department of Dermatology, Clinical Medicine School, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China
| | - Qian Wu
- Nursing School, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China
| | - Feng Wu
- Stomatology and Optometry School, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China
| | - Tonghui She
- Department of Pathology, Basic Medicine School, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China
| | - Ying Chu
- Department of Burn and Plastic Surgery, Enshi State Central Hospital, Enshi, Hubei 445099, P.R. China
| | - Qizhi Huang
- Department of Clinical Lab, Second Affiliated Hospital, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China
| | - Zhifeng Ning
- Department of Human Anatomy, Basic Medicine School, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China
| | - Hao Zhang
- Institute of Precision Cancer Medicine and Pathology, Department of Pathology, Jinan University Medical College, Guangzhou, Guangdong 510630, P.R. China
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