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1.
Sci Rep ; 13(1): 1060, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658180

RESUMO

Mutations at specific hotspots in non-coding regions of ADGRG6, PLEKHS1, WDR74, TBC1D12 and LEPROTL1 frequently occur in bladder cancer (BC). These mutations could function as biomarkers for the non-invasive detection of BC but this remains largely unexplored. Massively-parallel sequencing of non-coding hotspots was applied to 884 urine cell pellet DNAs: 591 from haematuria clinic patients (165 BCs, 426 non-BCs) and 293 from non-muscle invasive BC surveillance patients (29 with recurrence). Urine samples from 142 non-BC haematuria clinic patients were used to optimise variant calling. Non-coding mutations are readily detectable in the urine of BC patients and undetectable, or present at much lower frequencies, in the absence of BC. The mutations can be used to detect incident BC with 66% sensitivity (95% CI 58-75) at 92% specificity (95% CI 88-95) and recurrent disease with 55% sensitivity (95% CI 36-74) at 85% specificity (95% CI 80-89%) using a 2% variant allele frequency threshold. In the NMIBC surveillance setting, the detection of non-coding mutations in urine in the absence of clinically detectable disease was associated with an increased relative risk of future recurrence (RR = 4.62 (95% CI 3.75-5.48)). As urinary biomarkers, non-coding hotspot mutations behave similarly to driver mutations in BC-associated genes and could be included in biomarker panels for BC detection.


Assuntos
Hematúria , Neoplasias da Bexiga Urinária , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/urina , Bexiga Urinária , Mutação , Proteínas de Ligação a RNA/genética
2.
Int J Mol Sci ; 23(24)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36555747

RESUMO

Active surveillance (AS) is the best strategy for small renal masses (SRMs) management; however, reliable methods for early detection and disease aggressiveness prediction are urgently needed. The aim of the present study was to validate DNA methylation biomarkers for non-invasive SRM detection and prognosis. The levels of methylated genes TFAP2B, TAC1, PCDH8, ZNF677, FLRT2, and FBN2 were evaluated in 165 serial urine samples prospectively collected from 39 patients diagnosed with SRM, specifically renal cell carcinoma (RCC), before and during the AS via quantitative methylation-specific polymerase chain reaction. Voided urine samples from 92 asymptomatic volunteers were used as the control. Significantly higher methylated TFAP2B, TAC1, PCDH8, ZNF677, and FLRT2 levels and/or frequencies were detected in SRM patients' urine samples as compared to the control. The highest diagnostic power (AUC = 0.74) was observed for the four biomarkers panel with 92% sensitivity and 52% specificity. Methylated PCDH8 level positively correlated with SRM size at diagnosis, while TFAP2B had the opposite effect and was related to SRM progression. To sum up, SRMs contribute significantly to the amount of methylated DNA detectable in urine, which might be used for very early RCC detection. Moreover, PCDH8 and TFAP2B methylation have the potential to be prognostic biomarkers for SRMs.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Seguimentos , Biomarcadores , Metilação de DNA , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina
3.
BMC Cancer ; 22(1): 1195, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36403035

RESUMO

BACKGROUND: Early detection of bladder cancer (BCa) offers patients a favorable outcome and avoids the need for cystectomy. Development of an accurate and sensitive noninvasive BCa diagnostic test is imperative. DNA methylation is an early epigenetic event in the development of BCa. Certain specific aberrant methylations could serve as useful biomarkers. The aim of this study was to identify methylation biomarkers for early detection of BCa. METHODS: CpG methylation microarray analysis was conducted on primary tumors with varying stages (T1-T4) and paired nontumor tissues from nine BCa patients. Bisulfite-pyrosequencing was performed to confirm the methylation status of candidate genes in tissues and urine sediments (n = 51). Among them, PENK was selected as a potential candidate and validated using an independent set of 169 urine sediments (55 BCa, 25 benign urologic diseases, 8 other urologic cancers, and 81 healthy controls) with a quantitative methylation-specific real time PCR (mePENK-qMSP). All statistical analyses were performed using MedCalc software version 9.3.2.0. RESULTS: CpG methylation microarray analysis and stepwise validation by bisulfite-pyrosequencing for tissues and urine sediments supported aberrant methylation sites of the PENK gene as potential biomarkers for early detection of BCa. Clinical validation of the mePENK-qMSP test using urine sediment-DNA showed a sensitivity of 86.5% (95% CI: 71.2 - 95.5%), a specificity of 92.5% (95% CI: 85.7 - 96.7%), and an area under ROC of 0.920 (95% CI: 0.863 - 0.959) in detecting Ta high-grade and advanced tumor stages (T1-T4) of BCa patients. Sensitivities for Ta low-grade, Ta high-grade, T1 and T2-T4 were 55.6, 83.3, 88.5, and 100%, respectively. Methylation status of PENK was not correlated with sex, age or stage, while it was associated with the tumor grade of BCa. CONCLUSIONS: In this study, we analyzed the comprehensive patterns of DNA methylation identified that PENK methylation possesses a high potential as a biomarker for urine-based early detection of BCa. Validation of PENK methylation confirms that it could significantly improve the noninvasive detection of BCa.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Detecção Precoce de Câncer , DNA
4.
Sci Rep ; 12(1): 18452, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36323734

RESUMO

Two molecular cytology approaches, (i) time-gated immunoluminescence assay (TGiA) and (ii) Raman-active immunolabeling assay (RiA), have been developed to detect prostate cancer (PCa) cells in urine from five prostate cancer patients. For TGiA, PCa cells stained by a biocompatible europium chelate antibody-conjugated probe were quantitated by automated time-gated microscopy (OSAM). For RiA, PCa cells labeled by antibody-conjugated Raman probe were detected by Raman spectrometer. TGiA and RiA were first optimized by the detection of PCa cultured cells (DU145) spiked into control urine, with TGiA-OSAM showing single-cell PCa detection sensitivity, while RiA had a limit of detection of 4-10 cells/mL. Blinded analysis of each patient urine sample, using MIL-38 antibody specific for PCa cells, was performed using both assays in parallel with control urine. Both assays detected very low abundance PCa cells in patient urine (3-20 PCa cells per mL by TGiA, 4-13 cells/mL by RiA). The normalized mean of the detected PCa cells per 1 ml of urine was plotted against the clinical data including prostate specific antigen (PSA) level and Clinical Risk Assessment for each patient. Both cell detection assays showed correlation with PSA in the high risk patients but aligned with the Clinical Assessment rather than with PSA levels of the low/intermediate risk patients. Despite the limited available urine samples of PCa patients, the data presented in this proof-of-principle work is promising for the development of highly sensitive diagnostic urine tests for PCa.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Biomarcadores Tumorais/urina , Próstata , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/urina , Pelve
5.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36430798

RESUMO

Bladder cancer (BC) is the 10th most common cancer in the world. While there are FDA-approved urinary assays to detect BC, none have demonstrated sufficient sensitivity and specificity to be integrated into clinical practice. Telomerase Reverse Transcriptase (TERT) gene mutations have been identified as the most common BC mutations that could potentially be used as non-invasive urinary biomarkers to detect BC. This study aims to evaluate the validity of these tests to detect BC in the Kerman province of Iran, where BC is the most common cancer in men. Urine samples of 31 patients with primary (n = 11) or recurrent (n = 20) bladder tumor and 50 controls were prospectively collected. Total urinary DNA was screened for the TERT promoter mutations (uTERTpm) by Droplet Digital PCR (ddPCR) assays. The performance characteristics of uTERTpm and the influence by disease stage and grade were compared to urine cytology results. The uTERTpm was 100% sensitive and 88% specific to detect primary BC, while it was 50% sensitive and 88% specific in detecting recurrent BC. The overall sensitivity and specificity of uTERTpm to detect bladder cancer were 67.7% and 88.0%, respectively, which were consistent across different tumor stages and grades. The most frequent uTERTpm mutations among BC cases were C228T (18/31), C250T (4/31), and C158A (1/31) with mutant allelic frequency (MAF) ranging from 0.2% to 63.3%. Urine cytology demonstrated a similar sensitivity (67.7%), but lower specificity (62.0%) than uTERTpm in detecting BC. Combined uTERTpm and urine cytology increased the sensitivity to 83.8%, but decreased the specificity to 52.0%. Our study demonstrated promising diagnostic accuracy for the uTERTpm as a non-invasive urinary biomarker to detect, in particular, primary BC in this population.


Assuntos
Carcinoma de Células de Transição , Telomerase , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Masculino , Humanos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Telomerase/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Recidiva Local de Neoplasia/genética , Carcinoma de Células de Transição/patologia , Neoplasias Urológicas/genética , Mutação , RNA Polimerases Dirigidas por DNA/genética
6.
Anticancer Res ; 42(11): 5249-5256, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36288849

RESUMO

BACKGROUND/AIM: New luminometric chelates were developed for the detection of urinary bladder cancer and compared to cytology and urinary rapid tests BTA stat®, NMP22® BladderChek® and UBC® Rapid Test. MATERIALS AND METHODS: This single-center study analyzed urine from two different cohorts: Firstly, a retrospective pilot cohort (n=27) and secondly a prospective validation cohort (n=60) including patients with bladder cancer and healthy controls. The samples were studied with nine different terbium and europium chelates to detect cancer cases. After identification of an efficient luminophore in the first cohort, the second validation cohort was run with the selected chelates to re-evaluate the results and compare them with urinary rapid tests and cytology. RESULTS: The compared methods showed area under the curve (AUC) values ranging from 0.567 to 0.767. Tb3+-chelate-based assay detected high-grade cancer cases (p=0.035) with an AUC of 0.663. The Eu-probe signal level was higher in cancer cases of any grade than in healthy controls (p=0.001) with an AUC of 0.759. The Eu-probe had a sensitivity of 46.7% and a specificity of 100% in cancer detection. CONCLUSION: Evaluation of terbium and europium chelates for the detection of urinary bladder cancer showed highest specificity among all methods and improved overall performance (characterized by AUC) compared to commercial urine-based rapid tests and cytology. The Eu-probe has the potential to be clinically valuable in urine-based detection of bladder cancer, especially for high-grade cancer.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Biomarcadores Tumorais/urina , Carcinoma de Células de Transição/diagnóstico , Európio , Estudos Retrospectivos , Sensibilidade e Especificidade , Térbio , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina
7.
Biosens Bioelectron ; 218: 114764, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36206669

RESUMO

Urinary bladder cancer (UBC) is one of the most common cancers and has notoriously high risk of recurrence and mortality across the globe. Current clinical initial diagnostic approaches are either invasive or lacks sensitivity. In this study, an attempt has been made to invent a cost-effective, novel, portable diagnostic device based on the environmental sensitive fluorophores namely Nile Red (NR), Eosin Y (EY) and Rose Bengal (RB). They act as sensing agents for detecting volatile organic compounds (VOC) exclusively present in the urine sample of UBC patients and differentiate the UBC samples from the healthy control group. Upon exposure with a particular group of VOCs, a significant amount of increment in fluorescence intensities of NR, EY and RB were detected and recorded in our indigenously developed "NABIL" device. To check the performance of NABIL, the data collected from the device was compared with the conventional techniques by arranging a clinical trial with 21 healthy controls and 52 UBC patients. With the assistance of our analysis technique based on LabVIEW platform, very high sensitivity and accuracy from healthy controls have been achieved. For UBC patients, it shows impressive diagnostic results. In addition, depending on the sample processing mechanism, NABIL device can also reveal the grade of UBC and prognosis under treatment. Overall, this study contributes a novel, non-invasive, easy-to-use, inexpensive, real-time, accurate method for selectively UBC diagnosis, which can be useful for personalized care/diagnosis and postoperative surveillance, resulting in saving more lives.


Assuntos
Técnicas Biossensoriais , Neoplasias da Bexiga Urinária , Compostos Orgânicos Voláteis , Humanos , Biomarcadores , Biomarcadores Tumorais/urina , Amarelo de Eosina-(YS) , Rosa Bengala , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina
8.
Br J Cancer ; 127(11): 2043-2051, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36192490

RESUMO

BACKGROUND: Non-invasive urine-based biomarkers can potentially improve current diagnostic and monitoring protocols for bladder cancer (BC). Here we assess the performance of earlier published biomarker panels for BC detection (BC-116) and monitoring of recurrence (BC-106) in combination with cytology, in two prospectively collected patient cohorts. METHODS: Of the 602 patients screened for BC, 551 were found eligible. For the primary setting, 73 patients diagnosed with primary BC (n = 27) and benign urological disorders, including patients with macroscopic haematuria, cystitis and/or nephrolithiasis (n = 46) were included. In total, 478 patients under surveillance were additionally considered (83 BC recurrences; 395 negative for recurrence). Urine samples were analysed with capillary electrophoresis-mass spectrometry. The biomarker score was estimated via support vector machine-based software. RESULTS: Validation of BC-116 biomarker panel resulted in 89% sensitivity and 67% specificity (AUCBC-116 = 0.82). A diagnostic score based on cytology and BC-116 resulted in good (AUCNom116 = 0.85) but not significantly better performance (P = 0.5672). A diagnostic score including BC-106 and cytology was evaluated (AUCNom106 = 0.82), significantly outperforming both cytology (AUCcyt = 0.72; P = 0.0022) and BC-106 (AUCBC-106 = 0.67; P = 0.0012). CONCLUSIONS: BC-116 biomarker panel is a useful test for detecting primary BC. BC-106 classifier integrated with cytology showing >95% negative predictive value, might be useful for decreasing the number of cystoscopies during surveillance.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Biomarcadores Tumorais/urina , Estudos Prospectivos , Testes Diagnósticos de Rotina , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/urina , Peptídeos , Sensibilidade e Especificidade
9.
Clin Epigenetics ; 14(1): 115, 2022 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115961

RESUMO

BACKGROUND: Cystoscopy is the gold standard for bladder cancer detection, but is costly, invasive and has imperfect diagnostic accuracy. We aimed to identify novel and accurate DNA methylation biomarkers for non-invasive detection of bladder cancer in urine, with the potential to reduce the number of cystoscopies among hematuria patients. RESULTS: Biomarker candidates (n = 32) were identified from methylome sequencing of urological cancer cell lines (n = 16) and subjected to targeted methylation analysis in tissue samples (n = 60). The most promising biomarkers (n = 8) were combined into a panel named BladMetrix. The performance of BladMetrix in urine was assessed in a discovery series (n = 112), consisting of bladder cancer patients, patients with other urological cancers and healthy individuals, resulting in 95.7% sensitivity and 94.7% specificity. BladMetrix was furthermore evaluated in an independent prospective and blinded series of urine from patients with gross hematuria (n = 273), achieving 92.1% sensitivity, 93.3% specificity and a negative predictive value of 98.1%, with the potential to reduce the number of cystoscopies by 56.4%. CONCLUSIONS: We here present BladMetrix, a novel DNA methylation urine test for non-invasive detection of bladder cancer, with high accuracy across tumor grades and stages, and the ability to spare a significant number of cystoscopies among patients with gross hematuria.


Assuntos
Neoplasias da Bexiga Urinária , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Metilação de DNA , Hematúria/diagnóstico , Hematúria/genética , Humanos , Estudos Prospectivos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/urina
10.
World J Urol ; 40(10): 2387-2398, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36057894

RESUMO

PURPOSE: Bladder cancer (BC) is among the most frequent malignancies worldwide. Novel non-invasive markers are needed to diagnose and stage BC with more accuracy than invasive procedures like cystoscopy. To date, no study has identified urine metabolites characteristic of all BC stages. To discover novel urine metabolomic profiles to diagnose and stage non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) patients using mass spectrometry-based metabolomics. METHODS: We prospectively recruited 198 BC patients and 98 age- and sex-matched healthy volunteers without evidence of renal or bladder condition confirmed by ultrasound, from whom we collected a first morning urine sample (before surgery in patients). In a discovery stage, an untargeted metabolomic analysis was conducted in urine samples of a selection of 64 BC patients (19 TaG1, 11 TaG3, 20 T1G3, 12 T2G3, 1 T2G2, 1 T3G3) and 20 controls to identify dysregulated metabolites. Next, after exhaustive multivariate analysis, confirmed dysregulated metabolites were validated in an independent cohort of 134 BC patients (19 TaG1, 62 TaG2, 9 TaG3, 15 T1G2, 16 T1G3, 4 T2G2, 9 T2G3) and 78 controls. RESULTS: We validated p-cresol glucuronide as potential diagnostic biomarker for BC patients compared to controls (AUC = 0.79). For NMIBC, p-cresol glucuronide was valuable as staging biomarker (AUC = 0.803). And among NMIBCs, p-coumaric acid may be a potential specific staging biomarker for the TaG1 NMIBC; however, future validation experiments should be conducted once the precise version of the standard is commercially available. Remarkably, for MIBC we validated spermine as potential specific staging biomarker (AUC = 0.882). CONCLUSION: Ours is the first metabolomics study conducted in urine of a thoroughly characterized cohort comprising all stages of NMIBC, MIBC and healthy controls in which we identified non-invasive diagnostic and staging biomarkers. These may improve BC management, thus reducing the use of current harmful diagnostic techniques.


Assuntos
Neoplasias da Bexiga Urinária , Biomarcadores , Biomarcadores Tumorais/urina , Cromatografia Líquida , Cresóis , Glucuronídeos , Humanos , Espermina , Espectrometria de Massas em Tandem , Neoplasias da Bexiga Urinária/patologia
11.
Sci Rep ; 12(1): 14837, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050450

RESUMO

Majority of patients with indolent prostate cancer (PCa) can be managed with active surveillance. Therefore, finding biomarkers for classifying patients between indolent and aggressive PCa is essential. In this study, we investigated urinary marker panels composed of urinary glycopeptides and/or urinary prostate-specific antigen (PSA) for their clinical utility in distinguishing non-aggressive (Grade Group 1) from aggressive (Grade Group ≥ 2) PCa. Urinary glycopeptides acquired via data-independent acquisition mass spectrometry (DIA-MS) were quantitatively analyzed, where prostatic acid phosphatase (ACPP), clusterin (CLU), alpha-1-acid glycoprotein 1 (ORM1), and CD antigen 97 (CD97) were selected to be evaluated in various combinations with and without urinary PSA. Targeted parallel reaction monitoring (PRM) assays of the glycopeptides from urinary ACPP and CLU were investigated along with urinary PSA for the ability of aggressive PCa detection. The multi-urinary marker panels, combined via logistic regression, were statistically evaluated using bootstrap resampling and validated by an independent cohort. Majority of the multi-urinary marker panels (e.g., a panel consisted of ACPP, CLU, and Urinary PSA) achieved area under the curve (AUC) ranged from 0.70 to 0.85. Thus, multi-marker panels investigated in this study showed clinically meaningful results on aggressive PCa detection to separate Grade Group 1 from Grade Group 2 and above warranting further evaluation in clinical setting in future.


Assuntos
Biomarcadores Tumorais , Antígeno Prostático Específico , Neoplasias da Próstata , Biomarcadores Tumorais/urina , Glicopeptídeos , Humanos , Masculino , Próstata , Antígeno Prostático Específico/urina , Neoplasias da Próstata/diagnóstico
12.
Sci Rep ; 12(1): 11523, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35798816

RESUMO

We report an EN2-specific (Kd = 8.26 nM) aptamer, and a sensitive and specific enzyme-linked oligonucleotide assay (ELONA) for rapid and sensitive colorimetric detection of bladder and prostate cancer biomarker EN2 in urine. The assay relies on an aptamer-mediated hybridization chain reaction (HCR) to generate DNA nanostructures that bind to EN2 and simultaneously amplify signals. The assay can be performed within 2.5 h, and has a limit of detection of 0.34 nM in buffer and 2.69 nM in artificial urine. Moreover, this assay showed high specificity as it did not detect other urinary proteins, including biomarkers of other cancers. The proposed ELONA is inexpensive, highly reproducible, and has great chemical stability, so it may enable development of a simple, sensitive and accurate diagnostic tool to detect bladder and prostate cancers early.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias da Próstata , Anticorpos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Proteínas de Homeodomínio , Humanos , Masculino , Proteínas do Tecido Nervoso/urina , Oligonucleotídeos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/urina , Bexiga Urinária
13.
Anal Chem ; 94(27): 9894-9902, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35762528

RESUMO

The diagnosis of bladder cancer (BC) is currently based on cystoscopy, which is invasive and expensive. Here, we describe a noninvasive profiling method for carbonyl metabolic fingerprints in BC, which is based on a desorption, separation, and ionization mass spectrometry (DSI-MS) platform with N,N-dimethylethylenediamine (DMED) as a differential labeling reagent. The DSI-MS platform avoids the interferences from intra- and/or intersamples. Additionally, the DMED derivatization increases detection sensitivity and distinguishes carboxyl, aldehyde, and ketone groups in untreated urine samples. Carbonyl metabolic fingerprints of urine from 41 BC patients and 41 controls were portrayed and 9 potential biomarkers were identified. The mechanisms of the regulations of these biomarkers have been tentatively discussed. A logistic regression (LR) machine learning algorithm was applied to discriminate BC from controls, and an accuracy of 85% was achieved. We believe that the method proposed here may pave the way toward the point-of-care diagnosis of BC in a patient-friendly manner.


Assuntos
Neoplasias da Bexiga Urinária , Aldeídos , Biomarcadores , Biomarcadores Tumorais/urina , Humanos , Espectrometria de Massas , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina
14.
Biomarkers ; 27(6): 568-578, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35532038

RESUMO

BACKGROUND: Bladder cancer (BCa) is the most common cancer of the urinary system. Due to its high incidence and recurrence, as well as limited progress in the effective treatment, BCa is a challenge for today's medicine. MATERIALS AND METHODS: We used a set of chromogenic substrates to differentiate between the stages of bladder cancer progression (G1 (n = 10), G2 (n = 10), G3 (n = 10)). The proteolytic activity in individual the urine samples was determined by absorbance measurements. Then inhibitors of particular classes of enzymes were used to determine which enzymes dominate at a given stage of the neoplastic disease. RESULTS: The specific activity of enzymes in the urine of patients with confirmed bladder cancer was determined separately for three (G1, G2, G3) stages of the disease development. What is more, no activity was observed in urine of healthy people (n = 10). DISCUSSION: Research shows that specific enzymes are associated with the development of specific stages of cancer. We suspect that the differences in the proteolytic activity of urine samples are due to the presence of a different set of enzymes that are directly related to the particular stage of the disease. CONCLUSION: We obtained three substrates for monitoring individual stages of bladder cancer development.


Assuntos
Neoplasias da Bexiga Urinária , Biomarcadores Tumorais/urina , Humanos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/diagnóstico
15.
Br J Cancer ; 127(2): 329-336, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35352020

RESUMO

BACKGROUND: The diagnosis and surveillance of urothelial bladder cancer (UBC) require cystoscopy. There is a need for biomarkers to reduce the frequency of cystoscopy in surveillance; urinary volatile organic compound (VOC) analysis could fulfil this role. This cross-sectional study compared the VOC profiles of patients with and without UBC, to investigate metabolomic signatures as biomarkers. METHODS: Urine samples were collected from haematuria clinic patients undergoing diagnostic cystoscopy and UBC patients undergoing surveillance. Urinary headspace sampling utilised solid-phase microextraction and VOC analysis applied gas chromatography-mass spectrometry; the output underwent metabolomic analysis. RESULTS: The median participant age was 70 years, 66.2% were male. Of the haematuria patients, 21 had a new UBC diagnosis, 125 had no cancer. In the surveillance group, 75 had recurrent UBC, 84 were recurrence-free. A distinctive VOC profile was observed in UBC patients compared with controls. Ten VOCs had statistically significant abundances useful to classify patients (false discovery rate range 1.9 × 10-7-2.8 × 10-2). Two prediction models were evaluated using internal validation. An eight-VOC diagnostic biomarker panel achieved AUROC 0.77 (sensitivity 0.71, specificity 0.72). A six-VOC surveillance biomarker panel obtained AUROC 0.80 (sensitivity 0.71 and specificity 0.80). CONCLUSIONS: Urinary VOC analysis could aid the diagnosis and surveillance of UBC.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Compostos Orgânicos Voláteis , Idoso , Biomarcadores , Biomarcadores Tumorais/urina , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/urina , Estudos Transversais , Feminino , Hematúria , Humanos , Masculino , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Compostos Orgânicos Voláteis/urina
16.
Arthritis Res Ther ; 24(1): 77, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35346341

RESUMO

OBJECTIVE: There is an urgent need to identify novel biomarkers of LN to reflect renal histological changes. This study aims to investigate urinary G3BP levels in LN patients and their association with renal disease activity both clinically and pathologically. METHODS: This is a cross-sectional study. A total of 119 lupus nephritis patients were recruited. Thirty patients with chronic kidney diseases (CKD) and 27 healthy volunteers were also recruited as controls. Urinary G3BP was tested by ELISA. Renal histopathology was reviewed by an experienced renal pathologist. Other clinical variables were collected through chart review. RESULTS: The levels of uG3BP were significantly increased in active LN patients compared to those in inactive LN (p<0.001), CKD patients (p=0.01), and healthy controls (p<0.001). ROC analysis indicated a good discrimination ability of uG3BP to differentiate active LN from CKD patients (AUC=0.7), inactive LN (AUC=0.76), or healthy controls (AUC=0.87). uG3BP was positively correlated with SLEDAI (ρ=0.352, p<0.001), rSLEDAI (ρ=0.302, p<0.001), and SLICC RAS (ρ=0.465, p<0.001), indicating a role as a biomarker of disease activity. It also correlated with clinical parameters, including 24-h urine protein, ESR, and serum C3 levels. In patients with 24-h urine protein > 3.0 g/24h, uG3BP levels were higher in proliferative LN than in membranous LN (p=0.04). They could discriminate the two pathogenic types of LN (AUC=0.72), and they also positively correlated with AI (ρ=0.389, p=0.008) and scores of hyaline deposits (ρ=0.418, p=0.006). While in patients with 24-h urine protein ≤ 3.0 g/24h, uG3BP levels were not significantly different between proliferative and membranous LN, and there was no apparent relationship between uG3BP levels with AI or with scores of hyaline deposits, but they correlated positively with scores of cellular/fibrocellular crescents (ρ=0.328, p=0.04). CONCLUSION: uG3BP is a non-invasive biomarker for clinically and histologically reflecting disease activity. It is associated with active histological changes and can be used as a surrogate biomarker when the renal biopsy is impractical.


Assuntos
Antígenos de Neoplasias , Biomarcadores Tumorais , Rim , Nefrite Lúpica , Antígenos de Neoplasias/urina , Biomarcadores/metabolismo , Biomarcadores Tumorais/urina , Estudos Transversais , Galectina 3 , Humanos , Rim/patologia , Nefrite Lúpica/patologia
17.
BMC Cancer ; 22(1): 237, 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241014

RESUMO

BACKGROUND: Bladder cancer is one of the most common malignancies but the corresponding diagnostic methods are either invasive or limited in specificity and/or sensitivity. This study aimed to develop a urine-based methylation panel for bladder cancer detection by improving published panels and validate performance of the new panel with clinical samples. METHODS: Related researches were reviewed and 19 potential panels were selected. RRBS was performed on a cohort with 45 samples to reassess these panels and a new panel inherited best markers was developed. The new panel was applied with qMSP platform to 33 samples from the RRBS cohort and the results were compared to those of RRBS. Lastly, another larger cohort with 207 samples was used to validate new panel performance with qMSP. RESULTS: Three biomarkers (PCDH17, POU4F2 and PENK) were selected to construct a new panel P3. P3 panel achieved 100% specificity and 71% sensitivity with RRBS in corresponding cohort and then showed a better performance of 100% specificity and 84% sensitivity with qMSP platforms in a balanced cohort. When validated with 207-sample cohort, P3 with qMSP showed a performance of 97% specificity and 87% sensitivity which was modestly improved compared to the panels it derided from. CONCLUSIONS: Overall, the P3 panel achieved relatively high sensitivity and accuracy in bladder cancer detection.


Assuntos
Metilação de DNA , Detecção Precoce de Câncer/métodos , Urinálise/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Urina/química , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Caderinas/urina , Encefalinas/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Precursores de Proteínas/urina , Sensibilidade e Especificidade , Fator de Transcrição Brn-3B/urina
18.
Arch. esp. urol. (Ed. impr.) ; 75(2): 165-172, mar. 28, 2022.
Artigo em Espanhol | IBECS | ID: ibc-203678

RESUMO

INTRODUCCIÓN: El uso del antígenoprostático específico (PSA) es útil para el diagnósticodel cáncer de próstata. Su principal limitación es labaja especificidad, esto ha llevado a la búsqueda denuevos biomarcadores con el fin de identificar el cáncer de próstata clínicamente significativo y poder disminuir el sobrediagnóstico y sobretratamiento.El objetivo de este artículo es resumir la literaturaactual sobre los biomarcadores urinarios utilizados enel diagnóstico de cáncer de próstata.Se llevó a cabo una búsqueda bibliográfica en PubMed hasta diciembre del 2020. Hemos seleccionadolos artículos originales, ensayos clínicos y revisionesmás recientes que proporcionan información sobre eluso de biomarcadores.En esta revisión, hemos discutido cuatro importantes biomarcadores urinarios útiles para el diagnósticodel cáncer de próstata: PCA3, Select MDX, ExoDX, TMPRSS2:ERG.CONCLUSIÓN: El uso de biomarcadores urinariosha mejorado del diagnóstico de cáncer de próstata clínicamente significativo. Su uso reduce el número debiopsias innecesarias y evita el sobretratamiento delcáncer de próstata indolente. (AU)


INTRODUCTION: The use of prostatespecific antigen (PSA) is useful for the diagnosis ofprostate cancer. Its main limitation is its low specificity, which has led to the search for new biomarkersin order to identify clinically significant prostatecancer and to reduce overdiagnosis and overtreatment.The aim of this article is to summarize the current literature on urinary biomarkers used in thediagnosis of prostate cáncer.A PubMed-based literature search was conductedup to December 2020. We selected the most recentand relevant original articles, clinical trials and reviews that have provided relevant information onthe use of biomarkers.In this review, we have discussed four importanturinary biomarkers useful for prostate cancer diagnosis: PCA3, Select MDX, ExoDX, TMPRSS2:ERG.CONCLUSION: The use of urinary biomarkers hasimproved of clinically significant prostate cancerdiagnosis. Their use reduces the number of unnecessary biopsies and avoids overtreatment of indolent prostate cancer. (AU)


Assuntos
Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Biomarcadores Tumorais/urina , Antígeno Prostático Específico/urina , Sensibilidade e Especificidade
19.
BMC Cancer ; 22(1): 214, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35220945

RESUMO

Bladder cancer (BC) is one of the most frequent cancer in the world, and its incidence is rising worldwide, especially in developed countries. Urine metabolomics is a powerful approach to discover potential biomarkers for cancer diagnosis. In this study, we applied an ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) method to profile the metabolites in urine from 29 bladder cancer patients and 15 healthy controls. The differential metabolites were extracted and analyzed by univariate and multivariate analysis methods. Together, 19 metabolites were discovered as differently expressed biomarkers in the two groups, which mainly related to the pathways of phenylacetate metabolism, propanoate metabolism, fatty acid metabolism, pyruvate metabolism, arginine and proline metabolism, glycine and serine metabolism, and bile acid biosynthesis. In addition, a subset of 11 metabolites of those 19 ones were further filtered as potential biomarkers for BC diagnosis by using logistic regression model. The results revealed that the area under the curve (AUC) value, sensitivity and specificity of receiving operator characteristic (ROC) curve were 0.983, 95.3% and 100%, respectively, indicating an excellent discrimination power for BC patients from healthy controls. It was the first time to reveal the potential diagnostic markers of BC by metabolomics, and this will provide a new sight for exploring the biomarkers of the other disease in the future work.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Metabolômica/métodos , Espectrometria de Massas em Tandem/métodos , Urinálise/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/urina , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade
20.
Sci Rep ; 12(1): 2433, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165329

RESUMO

Assessment of risk for a given disease and the diagnosis of diseases is often based on assays detecting biomarkers. Antibody-based biomarker-assays for diseases such as prostate cancer are often ambiguous and biomarker proteins are frequently also elevated for reasons that are unspecific. We have opted to use luminescence modulating phages for the analysis of known acute inflammatory response biomarker CRP (C-reactive protein) and biomarkers of prostate cancer in urine samples. Firstly, CRP was used to simulate the detection process in a controlled chemical environment. Secondly, we tried to classify more challenging lethal prostate cancer samples from control samples. Our unique method utilizes a special biopanning process in order to create special phages capable of capturing a dye necessary for detection and potential biomarkers. As the biomarker-molecules interfere with the phages, dye is repelled from the phage network resulting in an altered reporter luminescence. These changes can be observed with an absorbance reader and even with the naked eye. The simple method could present an alternative for screening of disease biomarkers. For prostate cancer urine samples, we achieved a sensitivity of 80% and specificity of 75% to detect Grade Group (GG) 4 and 5 prostate cancer.


Assuntos
Bacteriófagos , Técnicas Biossensoriais/métodos , Medições Luminescentes/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/urina , Sistema de Registros , Bacteriófagos/metabolismo , Biomarcadores Tumorais/urina , Proteína C-Reativa/urina , Humanos , Calicreínas/urina , Masculino , Gradação de Tumores , Estudos Prospectivos , Antígeno Prostático Específico/urina , Estudos Retrospectivos , Sensibilidade e Especificidade
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