Biomarkers In Men Research Articles

Changes In Bone Turnover Biomarkers In Men And Women During Marine Corps Officer Candidates School

Changes In Bone Turnover Biomarkers In Men And Women During Marine Corps Officer Candidates School

Effect of Combined Low Dose Human Gonadotropic Hormone, Follicle Stimulating Hormone, and Testosterone Therapy (LFT Regimen) Versus Conventional High Dose Human Gonadotropic Hormone and Follicle Stimulating Hormone on Spermatogenesis and Biomarkers in Men With Hypogonadotropic Hypogonadism

ObjectiveIn male Congenital hypogonadotropic hypogonadism(CHH), it was observed that lower dose human gonadotropic hormone(hCG) can maintain normal intratesticular testosterone(ITT) levels. We propose this study to compare the Low-Dose hCG, follicle stimulating hormone(FSH), and Testosterone(T) [LFT Regimen] to conventional treatment to induce virilization and fertility. DesignThis open-label randomized pilot study was conducted from June 2020 to December 2021. Subjects and outcome measuresCHH were randomly assigned to either the LFT regimen (Group A)-low-dose hCG (500U thrice per week), FSH(150U thrice per week) and T(100mg biweekly) or conventional therapy(GroupB) with high hCG dose(2000U thrice per week) and the same FSH dose. The hCG dosage was titrated to reduce Anti-mullerian hormone(AMH) by 50% and normalization of plasma T in groups A and B, respectively. The primary objective was to compare the percentage of individuals who achieved spermatogenesis between the two groups. ResultsOut of 30 patients, 23(76·7%) subjects achieved spermatogenesis, and the median time was 12(9-14·9)months. There was no difference in achieving spermatogenesis between the two groups (64·3%vs87·5%,p=0·204), and even the median time for spermatogenesis was similar (15monthsvs12months,p=0·248). Both groups had non-significant median plasma AMH at spermatogenesis,[6·6ng/ml(3·3-9·76) vs 4·41ng/ml(2·3-6·47),p=0·298]. Similarly, the median plasma Inhibin B at spermatogenesis between groups were comparable[152·4pg/ml(101·7-198·0)vs149·1pg/ml(128·7-237·3),p=0·488]. ConclusionsA reasonable approach to induce fertility in male CHH is to initiate combination therapy using FSH, low-dose hCG targeting AMH <6·9 ng/ml, along with T to achieve normal range. Monitoring AMH could serve as a proxy indicator of spermatogenesis.

Inflammation, Immunonutritive, and Cardiovascular Risk Biomarkers in Men With Alcohol Use Disorder.

Alcohol Use Disorder (AUD) is a significant public health issue associated with serious health risks. This study aims to reveal the relationship between AUD and inflammatory, immunonutritive, and cardiovascular risk markers by evaluating hemogram and biochemistry parameters together in AUD. The data of 54 male patients with AUD and 45 male controls were included in the study. Sociodemographic-clinical data of the participants and Alcohol Use Disorders Identification Test (AUDIT) results were obtained from medical records. Systemic immune inflammation index (SII) was obtained with the platelet x neutrophil/lymphocyte formula; systemic immune response index (SIRI) was obtained with the monocyte x neutrophil/lymphocyte formula, plasma atherogenicity index (AIP) was obtained with the ratio of triglyceride to High-density Lipoprotein (HDL) cholesterol. C-Reactive Protein (CRP) albumin-lymphocyte (CALLY) index was obtained with the albumin x lymphocyte/CRP x 104 formula. Aspartate aminotransferase (AST), Gamma Glutamyl Transferase (GGT) activities, neutrophil, CRP, ferritin, SII, and SIRI levels were significantly higher in those with AUD compared to controls. Laboratory results of those with AUD were consistent with atherogenic dyslipidemia; higher triglyceride and total cholesterol levels and AIP values were found compared to controls. The amount of alcohol consumed was a predictor for high SII, SIRI, and AIP levels. The CALLY index, which evaluates immune function, inflammation, and nutritional status together, was significantly lower in patients compared to controls. The amount of alcohol use and the total AUDIT score were predictors for a low CALLY index. The results of this study support that AUD is a chronic inflammatory psychiatric disorder. We suggest that new inflammatory, immunonutritive, and cardiovascular biomarkersSII, SIRI, AIP, and CALLY index could be promising clinical tools to evaluate the severity, potential complications, and treatment response of AUD.

0033 Proteomic Profiling of Plasma Biomarkers in Men and Women with Diagnosed Insomnia

0033 Proteomic Profiling of Plasma Biomarkers in Men and Women with Diagnosed Insomnia

Breast cancer in men – histopathology and biomarkers

Breast cancer in men accounts for around 1% of all cases of the disease. The study aimed to identify histopathological parameters and selected biomarkers in men with breast cancer. Retrospective study of archival material from 53 men diagnosed with breast cancer at the department of pathology, Haukeland University Hospital, in the period 1996-2020. The prevalence of the oestrogen receptor (ER), progesterone receptor (PGR) and Human Epidermal Growth Factor (HER2) biomarkers was examined. Median age at time of diagnosis was 72 years. Median tumour diameter was 24mm. Forty-nine tumours were classified histologically as invasive carcinoma of no special type (NST), 29 tumours were histologic grade 2 and 18 were grade 3. Fifty-two tumours were ER positive, 39 were PGR positive and four were HER2 positive. Twenty-five patients had lymph node metastases. Our findings indicate that men with breast cancer are diagnosed at an older age than women, and that men have a more advanced stage than women at the time of diagnosis. The histopathology and expression of biomarkers of breast cancer differ between men and women.

Prognostic and predictive analyses of circulating plasma biomarkers in men with metastatic castration resistant prostate cancer treated with docetaxel/prednisone with or without bevacizumab.

CALGB 90401 (Alliance) was a phase III trial of 1050 patients with metastatic castration-resistant prostate cancer (mCRPC) comparing docetaxel, prednisone, bevacizumab (DP+B) versus DP alone. While this trial did not show an improvement in overall survival (OS), there were improved intermediate outcomes suggesting that subsets of men may derive benefit from this combination. The purpose of this analysis was to identify prognostic and predictive biomarkers associated with OS and progression-free survival (PFS) benefit from DP+B. Baseline EDTA plasma samples from 650 consenting patients were analyzed for 24 biomarkers. The proportional hazards model was utilized to test for the prognostic and predictive importance of the biomarkers for OS. The statistically significant biomarkers of OS were further investigated for prognostic and predictive importance for other secondary outcomes. 15 markers [ICAM-1, VEGF-R3, TIMP-1, TSP-2, Ang-2, Her-3, Osteopontin (OPN), PlGF, VCAM-1, HGF, VEGF, Chromogranin A, IL-6, VEGF-R1, BMP-9] were prognostic of OS, while 9 markers (ICAM-1, VEGF-R3, Her-3, TIMP-1, Ang-2, OPN, PlGF, HGF, and VEGF) were also prognostic of PFS. All markers were statistically significant in univariate analyses after adjustment for multiplicity (FDR < 0.1). In multivariable analyses of OS adjusting for risk score, seven markers had FDR < 0.1, including ICAM-1, VEGF-R3, TIMP-1, Ang-2, VEGF, TSP-2 and HGF. In unadjusted analysis, OPN was predictive of PFS improvement with DP+B, in both univariate and multivariable analysis. However, none of the biomarkers tested were predictive of clinical outcomes after adjusting for multiple comparisons. Multiple biomarkers were identified in CALGB 90401 as prognostic of clinical outcomes but not predictive of OS. While OPN may have promise as a potential biomarker for anti-angiogenic therapies, further mechanistic and clinical studies are needed to determine the underlying biology and potential clinical application.

Risk factor control and incident cardiovascular disease in patients with diabetes: Sex-specific relations.

Women with diabetes are at higher risk of cardiovascular diseases (CVD) than men with diabetes; however, the sex difference in the association between the degree of risk factor control and the risk of CVD in patients with diabetes is unclear. In total, 17 260 participants diagnosed with diabetes from the UK Biobank were included and matched with 86 300 non-diabetes controls based on age, sex and assessment centre. The main exposure was the number of risk factors within the target range, including glycated haemoglobin level <53 mol/mol (7%), blood pressure <140/90 mm/Hg, low-density lipoprotein cholesterol <100 mg/dl, non-current smoking and absence of microalbuminuria. During a median follow-up of 13.3 years, a total of 3338 incident CVD cases, including 2807 ischaemic heart disease and 793 strokes, were documented. A more stringent control of risk factors was significantly associated with a lower risk of incident CVD, and such an association was significantly stronger in women than men. Compared with non-diabetes participants, the diabetes-related risk of CVD appeared to be eliminated if more than three risk factors were well controlled among women and men with diabetes. Moreover, clinical biomarkers (e.g. glycated haemoglobin and blood pressure) showed greater relative importance than other factors in women, whereas socio-economic and psychological factors (e.g. education and depression) exhibited similar relative importance to clinical biomarkers in men with diabetes. Our findings highlighted the importance of raising awareness of sex differences in the management of CVD risk factors among patients with diabetes.

Investigating the relationship between non-occupational pesticide exposure and metabolomic biomarkers.

The relationship between pesticide exposures and metabolomics biomarkers is not well understood. We examined the changes in the serum metabolome (early biomarkers) and the metabolic pathways associated with various pesticide exposure scenarios (OPE: overall exposure, PEM: exposure in months, PEY: exposure in years, and PEU: reported specific pesticides use) using data from the Northern Finland Birth Cohort 1966 31-year cross-sectional examination. We utilized questionnaire data on pesticide exposures and serum samples for nuclear magnetic resonance (NMR)-based metabolomics analyses. For exposures and metabolites associations, participants size varied between 2,361 and 5,035. To investigate associations between metabolomics biomarkers and exposure to pesticide scenarios compared to those who reported no exposures multivariable regression analyses stratified by sex and adjustment with covariates (season of pesticide use, socioeconomic position (SEP), alcohol consumption, BMI, and latitude of residence) were performed. Multiple testing by Benjamini-Hochberg false discovery rate (FDR) correction applied. Pesticide exposures differed by sex, season of pesticide use, alcohol, SEP, latitude of residence. Our results showed that all pesticide exposure scenarios were negatively associated with decreased HDL concentrations across all lipoprotein subclasses in women. OPE, PEY, and PEU were associated with decreased branched-chain amino acid concentrations in men and decreased albumin concentrations in women. OPE, PEY and PEU were also associated with changes in glycolysis metabolites and ketone bodies in both sexes. Specific pesticides exposure was negatively associated with sphingolipids and inflammatory biomarkers in men. In women, OPE, PEM, and PEU were associated with decreased apolipoprotein A1 and increased apolipoprotein B/apolipoprotein A1 ratio. Our findings suggest that identification of early biomarkers of disease risk related to pesticide exposures can inform strategies to reduce exposure and investigate causal pathways. Women may be more susceptible to non-occupational pesticide exposures when compared to men, and future sex-specific studies are warranted.

Immunoaging - the effect of age on serum levels of NET biomarkers in men: a pilot study.

The study aimed to evaluate the impact of aging on the formation of neutrophil extracellular traps (NETs). The impaired formation of NETs is the cause of an abnormal innate immune response. The study included a total of 45 healthy male subjects of different age groups. Whole blood was collected from the subjects, and the concentration of myeloperoxidase (MPO), the main biocidal protein in NETs, was determined in serum using ELISA. The serum levels of circulating free DNA (cfDNA), which are the structural basis of NETs, were also measured by fluorescence. In addition, the white blood cell count was determined, whole blood smear was evaluated, and the neutrophillymphocyte ratio was calculated. The variations in the levels of NET biomarkers were analyzed in different age groups. The low levels of MPO (243.70 ng/ml) and cfDNA (6.24 ng/100 μl) in boys indicated neutrophil insufficiency for NETosis in children. A progressive increase in the levels of MPO and cfDNA with age was observed among adolescents (420.91, p = 0.04; 13.55, p = 0.03, respectively), with the highest level noted in the healthy adult group (466.58, p = 0.01; 14.07, p = 0.01, respectively). The levels of the studied parameters were comparable in adolescents and young adults, which proved that the NETosis process was appropriate and suggested the attainment of neutrophil maturity for the release of NETs in adolescence. The levels of MPO and cfDNA were low in older men (225.46, p < 0.01; 5.19, p < 0.01, respectively) indicating impaired NET formation. Data on the generation of NETs in different age groups obtained in this study can allow a better understanding of the ontogenesis of the immune system in terms of the course of NETosis, and also indicate the need to support nonspecific responses in children and adults. Further research should be performed to determine the possibility of regulating the NETosis process. Int J Occup Med Environ Health. 2023;36(3):333-48.

Association between urology practice use of multiparametric MRI and genomic testing and treatment of men with newly diagnosed prostate cancer

IntroductionBiomarkers for prostate cancer, such as multiparametric MRI (mpMRI) and tissue-based genomics, are increasingly used for treatment decision-making. Using biomarkers indiscriminately and thus ignoring competing risks of mortality may lead to treatment in some men who derive little clinical benefit. We assessed the relationship between urology practice use of biomarkers and subsequent treatment in men with newly diagnosed prostate cancer. MethodsWe used a 20% random sample of national Medicare data to perform a retrospective cohort study of men with newly diagnosed prostate cancer diagnosed from 2015 through 2019. Urology practice-level use of biomarkers was characterized based on urology practice propensity to use either biomarker after diagnosis (never, below median, above the median). Noncancer mortality risk within 10 years of diagnosis was calculated for all men. Multilevel models were used to assess the relationship between practice-level biomarker use and treatment by noncancer mortality risk. ResultsBetween 2015 and 2019, 1,764 (65%) urology practices used mpMRI and 897 (33%) used genomic testing for prostate cancer. Compared with urology practices never using each biomarker, those using mpMRI above the median (56% vs. 47%, P = 0.003) and tissue-based genomics below the median (56% vs. 50%, P = 0.03) were more likely to treat men with >75% risk of noncancer mortality. Additionally, compared with urology practices never using either biomarker, use of mpMRI (72% vs. 69%, P = 0.07) or tissue-based genomics (71% vs. 70%, P = 0.65) did not impact treatment in the healthiest group (i.e., those with <25% risk of noncancer mortality). ConclusionsCompared to practices that do not use each biomarker in men with newly diagnosed prostate cancer, urology practices using mpMRI, and tissue-based genomics to a lesser extent, are more likely to treat men at very high risk of dying from competing risks of mortality within 10 years of prostate cancer diagnosis.

Use of Urinary Biomarkers in Discriminating Interstitial Cystitis/Bladder Pain Syndrome from Male Lower Urinary Tract Dysfunctions.

To analyze the urinary biomarkers in men with lower urinary-tract symptoms (LUTS) and identify interstitial cystitis/bladder pain syndrome (IC/BPS) from the other lower urinary-tract dysfunctions (LUTDs) by the levels of characteristic urinary biomarkers. In total, 198 men with LUTS were prospectively enrolled and urine samples were collected before intervention or medical treatment. Videourodynamic studies were routinely performed and the LUTDs were diagnosed as having bladder-outlet obstruction (BOO) such as bladder-neck dysfunction, benign prostatic obstruction, or poor relaxation of external sphincter (PRES); and bladder dysfunction such as detrusor overactivity (DO), hypersensitive bladder (HSB), and IC/BPS. Patients suspicious of IC/BPS were further confirmed by cystoscopic hydrodistention under anesthesia. The urine samples were investigated for 11 urinary inflammatory biomarkers including eotaxin, IL-6, IL-8, CXCL10, MCP-1, MIP-1β, RANTES, TNF-α, NGF, BDNF, and PGE2; and 3 oxidative stress biomarkers 8-OHdG, 8-isoprostane, and TAC. The urinary biomarker levels were analyzed between LUTD subgroups and IC/BPS patients. The results of this study revealed that among the patients, IC/BPS was diagnosed in 48, BOO in 66, DO in 25, HSB in 27, PRES in 15, and normal in 17. Patients with BOO had a higher detrusor pressure and BOO index than IC/BPS, whereas patients with IC/BPS, BOO, and DO had a smaller cystometric bladder capacity than the PRES and normal subgroups. Among the urinary biomarkers, patients with IC/BPS had significantly higher levels of eotaxin, MCP-1, TNF-α, 8-OHdG, and TAC than all other LUTD subgroups. By a combination of different characteristic urinary biomarkers, TNF-α, and eotaxin, either alone or in combination, had the highest sensitivity, specificity, positive predictive value, and negative predictive value to discriminate IC/BPS from patients of all other LUTD subgroups, BOO, DO, or HSB subgroups. Inflammatory biomarker MCP-1 and oxidative stress biomarkers 8-OHdG and TAC, although significantly higher in IC/BPS than normal and PRES subgroups, did not have a diagnostic value between male patients with IC/BPS and the BOO, DO, or HSB subgroups. The study concluded that using urinary TNF-α and eotaxin levels, either alone or in combination, can be used as biomarkers to discriminate patients with IC/BPS from the other LUTD subgroups in men with LUTS.

Abstract B052: Prostate cancer prevention is possible thanks to the evaluation of the primary exons of the BRCA1 biomarker in men

Abstract Prostate cancer is a public health concern among 50 year old the men worldwide and its incidence keep rising. It is triggered by genome instability or epigenetic modifications impacting DNA repair and tumor suppression genes and proteins. In African countries, little data is available on prostate cancer and the loss of BRCA1 exons responsible for tumor suppression. It is in this context that we undertook this study, the general objective of which is to assess the association between BRCA1 instability in patients with prostate cancer, These men with prostate cancer usually present with symptoms like nocturia and poor urinary flow, erectile dysfunction and visible hematuria. Citation Format: Haboubacar Elhadji Yaou Moussa, Callinis Capo Chichi. Prostate cancer prevention is possible thanks to the evaluation of the primary exons of the BRCA1 biomarker in men [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B052.

Novel approaches to redesign surveillance strategies following orchiectomy for localized testicular cancer: a narrative review.

Surveillance is the preferred management strategy for most men with clinical stage I testicular cancer after orchiectomy. However, frequent office visits, imaging tests, and laboratory studies place a significant burden on patients, which may contribute to poor compliance with guideline-recommended surveillance regimens. Identifying strategies to overcome these barriers may help improve quality of life, reduce costs, and improve adherence for patients. We reviewed evidence for three strategies that may help with surveillance redesign: telemedicine, implementing microRNA (miRNA) as a biomarker, and novel imaging protocols. A web-based literature search for novel imaging strategies, diagnostic utility of miRNA, and telehealth as they relate to early-stage testicular germ cell cancer was completed during the month of August 2022. We focused our search on contemporary PubMed-indexed and Google Scholar-registered manuscripts written in English. Supportive data sourced from current guideline statements were also included. Evidence was compiled for narrative review. Telemedicine is a safe and acceptable platform for urologic cancer follow-up care, but it requires further study specifically among men with testicular cancer. Access to care may either be improved or reduced depending on system- and patient-level characteristics and should be implemented with this in mind. miRNA may potentially be a helpful biomarker for men with localized disease, but further research on diagnostic accuracy and marker kinetics are needed before implementing it into routine surveillance strategies or using it to deviate from long-standing surveillance regiments. Novel imaging strategies with less frequent imaging and the use of magnetic resonance imaging (MRI) instead of computed tomography (CT) appear to be non-inferior in clinical trials. However, use of MRI requires expert radiologist availability and may be more costly with a lower ability to detect small, early recurrences when used in routine practice. Using telemedicine, integrating miRNA as a tumor marker, and adopting less intensive imaging strategies may improve guideline-concordant surveillance for men with localized testicular cancer. Future studies are needed to assess the risks and benefits of using these novel approaches separately or together.

Blood microRNA-7 as a Progression Biomarker in men with Parkinson's disease (S37.006)

<h3>Objective:</h3> To investigate the use of microRNA-7-5p (miR-7-5p) as a potential biomarker for Parkinson9s disease (PD) progression. <h3>Background:</h3> Animal models have shown that MiR-7-5p regulates alpha-synuclein (α-syn) translation, transcription and autophagy, in addition to NLRP3 inflammasome activity. Furthermore, MiR-7-5p is diminished in the substantia nigra and the peripheral blood of PD patients. <h3>Design/Methods:</h3> Data was obtained at two longitudinal points (Baseline and 36 months) from 315 (208 male/107 female) drug-naïve PD patients and 160 (108 male /52 female) age- and sex-matched healthy controls (HC) from the Parkinson9s Progression Marker Initiative (PPMI). Whole blood miR-7-5p was longitudinally correlated with a) clinical assessment tools (MDS-UPDRS motor and total scores), b) markers of inflammation (NLRP3 mRNA, IL-1β mRNA, and NfL), and c) α-syn expression (α-syn mRNA, CSF α-syn). Analyses were done using rmcorr in R. <h3>Results:</h3> MiR-7-5p levels decreased by 17% in PD patients over 36 months. Longitudinal, Ln miR-7-5p had a strong negative correlation with MDS-UPDRS-motor and total scores in men with PD and with NfL for all PD subjects. There was no correlation between miR-7-5p and CSF α-syn protein in either group. <h3>Conclusions:</h3> Our data demonstrate the importance of gender differences in biomarker discovery and suggest a robust association between lower levels of miR-7-5p and markers of clinical progression in men with PD. These findings support the use of miR-7-5p as a progression biomarker, which could lead to a quantifiable tool for disease-modifying therapies. <b>Disclosure:</b> Dr. Schiess has nothing to disclose. Dr. Suescun has nothing to disclose. Dr. Block has nothing to disclose. Dr. Tharp has nothing to disclose. The institution of Prof. Ellmore has received research support from NIMH. The institution of Dr. Shahnawaz has received research support from American Parkinson Disease Association. The institution of Dr. Shahnawaz has received research support from NIH. The institution of Dr. Shahnawaz has received research support from Texas Alzheimer’s Research &amp; Care Consortium . Dr. Shahnawaz has received intellectual property interests from a discovery or technology relating to health care. Dr. Adams has stock in Medtronic.

Abstract 6507: E3 ubiquitin-protein ligase, tetratricopeptide repeat domain 3 (TTC3), H4 clustered histone 5 (H4C5), and epithelial cell adhesion molecule (EpCAM) are novel urine-enriched liquid biopsy biomarkers to detect prostate cancer in men

Abstract Background: Prostate Cancer (PCa) is one of the leading causes of cancer deaths among American men; however, the estimated number of diagnoses represents a small fraction of disease-related biopsies performed yearly. Although the Prostate-Specific Antigen (PSA) test is widely used for screening, several advisory groups recommend against using PSA because of its suboptimal performance. Thus, there is an urgent unmet need for novel and more accurate diagnostic biomarkers for PCa detection and to differentiate aggressive cancer from its indolent form. Methods: In our study, we used voided urine (50ml) from pre and post-prostatectomy men with PCa and urine from normal healthy men as control. We isolated RNA from exfoliated cells and debris shed into urine and performed RNA-sequencing using the Illumina Next-seq 550 platform. Advanced computational and machine-learning approaches were employed to identify candidate biomarkers in men with PCa. We examined the TCGA database to validate the PCa-specific expression of the identified RNA in tumor tissues. Two RNA markers were further tested by qPCR, and one urinary soluble protein marker was measured by immunoassays. Results: Our study included 106 men with PCa and 88 control men. We identified and validated the presence of ≥1 RNA markers (TTC3, H4C5) and a protein marker (EpCAM) in urine as potential candidate biomarkers for PCa detection. We tested and developed these markers using qPCR for TTC3, H4C5, and ELISA assay for EpCAM with higher specificity and sensitivity (Table 1). Our results outperformed known urinary markers, PCA3 and SPDEF (Figure 1). TTC3, H4C5, and EpCAM markers diminished to low or undetectable levels in post-prostatectomy compared to pre-prostatectomy men with PCa. shRNA knockdown of TTC3 and EpCAM in androgen-sensitive and insensitive cells induced biological changes, suggesting their relevance to Prostate Cancer. Conclusions: We report a highly accurate panel of 3 urine-based biomarkers that detect PCa consisting of EpCAM (protein) and TTC3 and H4C5 (RNA). To identify the advantage of using individual or combinatorial markers is an ongoing study in our laboratory. Citation Format: Ranjan Joseph Perera, Marcio Moschovas, Roshane Perera, Bongyong Lee, Alexandra Miller, Ernest K. Amankwah, Rudramani Pokhrel, Christian Pavlovich, Guru Sonpavde, Vipul Patel. E3 ubiquitin-protein ligase, tetratricopeptide repeat domain 3 (TTC3), H4 clustered histone 5 (H4C5), and epithelial cell adhesion molecule (EpCAM) are novel urine-enriched liquid biopsy biomarkers to detect prostate cancer in men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6507.

MP44-18 E3 UBIQUITIN-PROTEIN LIGASE, TETRATRICOPEPTIDE REPEAT DOMAIN 3 (TTC3), H4 CLUSTERED HISTONE 5 (H4C5), AND EPITHELIAL CELL ADHESION MOLECULE (EPCAM) ARE NOVEL URINE-ENRICHED LIQUID BIOPSY BIOMARKERS TO DETECT PROSTATE CANCER IN MEN

You have accessJournal of UrologyCME1 Apr 2023MP44-18 E3 UBIQUITIN-PROTEIN LIGASE, TETRATRICOPEPTIDE REPEAT DOMAIN 3 (TTC3), H4 CLUSTERED HISTONE 5 (H4C5), AND EPITHELIAL CELL ADHESION MOLECULE (EPCAM) ARE NOVEL URINE-ENRICHED LIQUID BIOPSY BIOMARKERS TO DETECT PROSTATE CANCER IN MEN Menglang Yuan, Marcio Moschovas, Roshane Perera, Bongyong Lee, Alexandra Miller, Ernest Amankwah, Rudramani Pokhrel, Christian Pavlovich, Guru Sonpavde, Vipul Patel, and Ranjan Perera Menglang YuanMenglang Yuan More articles by this author , Marcio MoschovasMarcio Moschovas More articles by this author , Roshane PereraRoshane Perera More articles by this author , Bongyong LeeBongyong Lee More articles by this author , Alexandra MillerAlexandra Miller More articles by this author , Ernest AmankwahErnest Amankwah More articles by this author , Rudramani PokhrelRudramani Pokhrel More articles by this author , Christian PavlovichChristian Pavlovich More articles by this author , Guru SonpavdeGuru Sonpavde More articles by this author , Vipul PatelVipul Patel More articles by this author , and Ranjan PereraRanjan Perera More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003290.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate Cancer (PCa) is one of the leading causes of cancer deaths among American men; however, the estimated number of diagnoses represents a small fraction of disease-related biopsies performed yearly. Although the Prostate-Specific Antigen (PSA) test is widely used for screening, several advisory groups recommend against using PSA because of its suboptimal performance. Thus, there is an urgent unmet need for novel and more accurate diagnostic biomarkers for PCa detection and to differentiate aggressive cancer from its indolent form. METHODS: In our study, we used voided urine (50ml) from pre and post-prostatectomy men with PCa and urine from normal healthy men as control. We isolated RNA from exfoliated cells and debris shed into urine and performed RNA-sequencing using the Illumina Next-seq 550 platform. Advanced computational and machine-learning approaches were employed to identify candidate biomarkers in men with PCa. We examined the TCGA database to validate the PCa-specific expression of the identified RNA in tumor tissues. Two RNA markers were further tested by qPCR, and one urinary soluble protein marker was measured by immunoassays. RESULTS: Our study included 106 men with PCa and 88 control men. We identified and validated the presence of ≥1 RNA markers (TTC3, H4C5) and a protein marker (EpCAM) in urine as potential candidate biomarkers for PCa detection. We tested and developed these markers using qPCR for TTC3, H4C5, and ELISA assay for EpCAM with higher specificity and sensitivity (Table 1). Our results outperformed known urinary markers, PCA3 and SPDEF (Figure 1). TTC3, H4C5, and EpCAM markers diminished to low or undetectable levels in post-prostatectomy compared to pre-prostatectomy men with PCa. shRNA knockdown of TTC3 and EpCAM in androgen-sensitive and insensitive cells induced biological changes, suggesting their relevance to Prostate Cancer. CONCLUSIONS: We report a highly accurate panel of 3 urine-based biomarkers that detect PCa consisting of EpCAM (protein) and TTC3 and H4C5 (RNA). To identify the advantage of using individual or combinatorial markers is an ongoing study in our laboratory. Source of Funding: Florida Department of Health, Bankhead-Coley Cancer Research Program 5BC08 to RJP. International Prostate Cancer Foundation (IPCF) to R.J.P and VP. National Institutes of Health grant NCI 5P30CA030199 to RJP © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e619 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Menglang Yuan More articles by this author Marcio Moschovas More articles by this author Roshane Perera More articles by this author Bongyong Lee More articles by this author Alexandra Miller More articles by this author Ernest Amankwah More articles by this author Rudramani Pokhrel More articles by this author Christian Pavlovich More articles by this author Guru Sonpavde More articles by this author Vipul Patel More articles by this author Ranjan Perera More articles by this author Expand All Advertisement PDF downloadLoading ...

Frailty and Alzheimer’s Disease Related Plasma Biomarkers in Men from Midlife to Early Old Age

AbstractBackgroundAbout 7 million older American adults are affected by frailty (Bandeen‐Roche et al., 2015). Frailty places older adults at an increased risk of adverse physical and mental health outcomes, including Alzheimer’s Disease (AD). However, prior to old age, frailty or its relationship to AD biomarkers such as beta‐amyloid 40 and 42 (Aβ40, Aβ42), tau, and neurofilament light (NfL) are understudied.MethodParticipants in this prospective longitudinal observational study were community‐based men of predominantly European ancestry. Data were collected across 3 waves at average ages 56 (2002‐08), 62 (2009‐14), and 68 (2016‐19). We calculated frailty index (FI) scores using 37 out of 49 items from an index previously validated in the UK Biobank (Williams et al. 2019; Jiang et al. 2017) which assesses health deficits across multiple physiological systems. FI is calculated as a proportion of deficits out of the total, with scores ranging from 0 (no deficits) to 1 (all deficits present). AD‐related plasma biomarkers for Aβ40,and Aβ42, total tau, and NfL were assayed at average ages 56 and 68. Biomarker values were adjusted for study site and storage time.ResultAverage FI score at age 56 was .2, equivalent to having about 7 health deficits. Frailty was significantly correlated (rs=.67‐.74) over time. Higher frailty at both age 56 and 62 doubled the risk for mortality across the 12 years of the study. Age 56 frailty was significantly associated with age 56 tau. Age 68 frailty was significantly associated with age 68 NfL, tau, Aβ40 and Aβ42. In models adjusted for age, education, and ethnicity, age 56 frailty predicted age 68 NfL (B=0.64, t=2.72, p=0.007); associations with age 68 Aβ40 (B=0.39, t=1.96, p=0.0513) and Aβ42 were attenuated (B=0.27, t=1.79, p=0.0743). Age 62 frailty mediated associations between age 56 tau and age 68 tau and NfL, but not other biomarkers.ConclusionThe results are striking given the relatively young age of the sample. Even as early as one’s 50s, links between frailty and increased risk for AD emerged. Public health groups have recommended routine frailty screening in adults over 65, but it may be important to start screenings earlier.

Gender Differences Contribute to Variability of Serum Lipid Biomarkers for Alzheimer'S Disease

Background: Alzheimer's disease (AD) cannot currently be diagnosed by a blood test. One reason may be gender differences. Another may be the statistical methods used. The authors evaluate these possibilities. Objective: The authors applied serum lipidomics to find AD biomarkers in men and women. They hypothesized that AD biomarkers would differ between genders and that machine-learning algorithms would improve diagnostic performance. Methods: Serum lipids were analyzed by mass spectrometry for a training set of AD cases and controls and in a blinded test set. Statistical analyses considered gender differences. Results: Lipids best classifying AD subjects differed significantly between men and women. Robust statistical algorithms did not improve diagnostic performance. Conclusion: Poor performance of AD biomarkers appears to be due primarily to inherent variability in AD patients.

Liquid biomarkers for early detection of prostate cancer and summary of available data for their use in African-American men.

Several liquid biomarker tests have been developed to account for the limitations of prostate specific antigen (PSA) screening prior to prostate biopsy. African ancestry is an established risk factor for prostate cancer (PCa) and must be particularly considered when evaluating patients with liquid biomarkers. While multiple tests have been developed over decades of exploration, recent advances can help patients and physicians incorporate data into a broader clinical context. We sought to review currently available liquid biomarker tests in a practical, clinically directed fashion with particular focus on performance in men with African ancestry. We reviewed discovery and validation studies and highlight important considerations for each test. We discuss the advantages and limitations of percent free PSA, Prostate Health Index, Progensa® PCA3, ExoDx® Prostate Test, SelectMDx®, 4Kscore® Test, and Mi-Prostate Score and summarize salient studies on their use. A literature review of evidence specifically for men with African ancestry was conducted and available studies were summarized. Liquid biomarkers can be useful tools for aiding in risk stratification prior to prostate biopsy. Use of such tests should be individualized based on a thorough knowledge of supporting evidence and the goals of the patient and physician. Further study should prioritize evaluation of such biomarkers in men with African ancestry.

Effect of Non-alcoholic Fatty Liver Disease on Some of Bone Biomarkers in Men

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the common liver diseases worldwide that is not associated with alcohol consumption; it is a group of disorders caused by fat accumulation in the liver. AIM: The research aims to assess the levels of serum sialoprotein, sclerostin, and osteocalcin in men with NAFLD. METHODS: The current study was conducted in Basra city, Iraq in 2020, which includes 400 men with NAFLD, age ranges between (30 and 50) years, and 400 matched health men as controls, serum levels of study parameters were measured using the ELISA method. RESULTS: The results showed a significant decrease in the levels of serum osteocalcin but a non-significant difference in sclerostin and bone sialoprotein in men with NAFLD comparing with the control group, also age and disease severity factors did not show any significant effect on study parameters in the patient’s group. CONCLUSION: In conclusion, men with NAFLD may be prone to some disturbances in the bone health regardless of disease progression and age in Basrah city.