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Wang X, Zhang L, Cheng L, Wang Y, Li M, Yu J, Ma Z, Ho PCL, Sethi G, Chen X, Wang L, Goh BC. Extracellular vesicle-derived biomarkers in prostate cancer care: Opportunities and challenges. Cancer Lett 2024; 601:217184. [PMID: 39142499 DOI: 10.1016/j.canlet.2024.217184] [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: 06/27/2024] [Revised: 08/04/2024] [Accepted: 08/07/2024] [Indexed: 08/16/2024]
Abstract
Prostate cancer (PCa) is the second most prevalent cancer in men worldwide, presenting a significant global public health challenge that necessitates early detection and personalized treatment. Recently, non-invasive liquid biopsy methods have emerged as promising tools to provide insights into the genetic landscape of PCa and monitor disease progression, aiding decision-making at all stages. Research efforts have concentrated on identifying liquid biopsy biomarkers to improve PCa diagnosis, prognosis, and treatment prediction. This article reviews recent research advances over the last five years utilizing extracellular vesicles (EVs) as a natural biomarker library for PCa, and discusses the clinical translation of EV biomarkers, including ongoing trials and key implementation challenges. The findings underscore the transformative role of liquid biopsy, particularly EV-based biomarkers, in revolutionizing PCa diagnosis, prediction, and treatment.
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Affiliation(s)
- Xiaoxiao Wang
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Limin Zhang
- Jingzhou Hospital of Traditional Chinese Medicine, Jingzhou, 434000, China; The Third Clinical Medical College of Yangtze University, Jingzhou, 434000, China
| | - Le Cheng
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Yufei Wang
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Mengnan Li
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Jiahui Yu
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Zhaowu Ma
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Paul Chi-Lui Ho
- School of Pharmacy, Monash University Malaysia, 47500, Subang Jaya, Malaysia
| | - Gautam Sethi
- NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore
| | - Xiaoguang Chen
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China.
| | - Lingzhi Wang
- NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
| | - Boon-Cher Goh
- NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore; Department of Haematology-Oncology, National University Cancer Institute, 119228, Singapore
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Raza A, Nawaz SH, Rashid R, Ahmed E, Mubarak M. The correlation of spot urinary protein-to-creatinine ratio with 24-h urinary protein excretion in various glomerulopathies. World J Nephrol 2023; 12:159-167. [PMID: 38230302 PMCID: PMC10789082 DOI: 10.5527/wjn.v12.i5.159] [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: 08/05/2023] [Revised: 09/21/2023] [Accepted: 10/23/2023] [Indexed: 12/22/2023] Open
Abstract
BACKGROUND Proteinuria is an important and well-known biomarker of many forms of kidney injury. Its quantitation is of particular importance in the diagnosis and management of glomerular diseases. Its quantification can be done by several methods. Among these, the measurement of 24-h urinary protein excretion is the gold standard method. However, it is cumbersome, time-consuming, and inconvenient for patients and is not completely foolproof. Many alternative methods have been tested over time albeit with conflicting results. Among the latter, the measurement of urine protein-to-creatinine ratio (uPCR) in single-voided urinary samples is widely used. The majority of studies found a good correlation between uPCR in single urine samples with 24-h urinary protein estimation, whereas others did not. AIM To investigate the correlation of spot uPCR with 24-h urinary protein estimation in patients suffering from different forms of glomerulopathies at a single large-volume nephrological center in Pakistan. METHODS This cross-sectional, observational study was conducted at the Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan from September 2017 to March 2018. All newly presenting adult patients with proteinuria who were being investigated for suspected glomerulonephritis and persistent proteinuria with ages between 18 to 60 years were enrolled. All patients were given detailed advice regarding 24-h urine collection starting at 7:00 AM for total protein and creatinine excretion estimations. A spot urine sample was collected the next day at the time of submission of a 24-h urine sample for measuring uPCR along with a blood sample. The data of patients were collected in a proforma. SPSS version 20.0 was used for statistical analysis. RESULTS A total of 157 patients were included. Their mean age was 30.45 ± 12.11 years. There were 94 (59.8%) males and 63 (40.2%) females. The mean 24-h urinary protein excretion was 3192.78 ± 1959.79 mg and the mean spot uPCR was 3.16 ± 1.52 in all patients. A weak but significant correlation was observed between spot uPCR and 24-h urinary protein excretion (r = 0.342, P = 0.01) among all patients. On subgroup analysis, a slightly better correlation was found in patients older than 47 years (r = 0.78), and those with body mass index > 25 kg/m2 (r = 0.45). The Bland and Altman's plot analysis comparing the differences between spot uPCR and 24-h protein measurement also showed a wide range of the limits of agreement between the two methods. CONCLUSION Overall, the results from this study showed a significant and weakly positive correlation between spot uPCR and 24-h urinary protein estimation in different forms of glomerulopathies. The agreement between the two methods was also poor. Hence, there is a need for careful interpretation of the ratio in an unselected group of patients with kidney disease.
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Affiliation(s)
- Amber Raza
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Sindh, Karachi 74200, Pakistan
| | - Syed Haider Nawaz
- Department of Pathology, Sindh Institute of Urology and Transplantation, Sindh, Karachi 74200, Pakistan
| | - Rahma Rashid
- Department of Pathology, Sindh Institute of Urology and Transplantation, Sindh, Karachi 74200, Pakistan
| | - Ejaz Ahmed
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Sindh, Karachi 74200, Pakistan
| | - Muhammed Mubarak
- Department of Pathology, Sindh Institute of Urology and Transplantation, Sindh, Karachi 74200, Pakistan
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Vago R, Radano G, Zocco D, Zarovni N. Urine stabilization and normalization strategies favor unbiased analysis of urinary EV content. Sci Rep 2022; 12:17663. [PMID: 36271135 PMCID: PMC9587215 DOI: 10.1038/s41598-022-22577-3] [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: 02/25/2022] [Accepted: 10/17/2022] [Indexed: 01/18/2023] Open
Abstract
Urine features an ideal source of non-invasive diagnostic markers. Some intrinsic and methodological issues still pose barriers to its full potential as liquid biopsy substrate. Unlike blood, urine concentration varies with nutrition, hydration and environmental factors. Urine is enriched with EVs from urinary-genital tract, while its conservation, purification and normalization can introduce bias in analysis of EV subsets in inter-and intra-individual comparisons. The present study evaluated the methods that decrease such biases such as appropriate and feasible urine storage, optimal single-step EV purification method for recovery of proteins and RNAs from small urine volumes and a normalization method for quantitative analysis of urine EV RNAs. Ultracentrifugation, chemical precipitation and immuno-affinity were used to isolate EVs from healthy donors' urine that was stored frozen or at room temperature for up to 6 months. Multiple urine biochemical and EV parameters, including particle count and protein content, were compared across urine samples. To this purpose nanoparticle tracking analysis (NTA) and protein assessment by BCA, ELISA and WB assays were performed. These measurements were correlated with relative abundances of selected EV mRNAs and miRNAs assessed by RT-PCR and ranked for the ability to reflect and correct for EV content variations in longitudinal urine samples. All purification methods enabled recovery and downstream analysis of EVs from as few as 1 ml of urine. Our findings highlight long term stability of EV RNAs upon urine storage at RT as well as excellent correlation of EV content in urine with some routinely measured biochemical features, such as total urine protein and albumin, but not creatinine most conventionally used for urine normalization. Comparative evaluation of mRNA and miRNAs in EV isolates revealed specific RNAs, in particular RNY4 and small miRNA panel, levels of which well reflected the inter-sample EV variation and therefore useful as possible post-analytical normalizers of EV RNA content. We describe some realistic urine processing and normalization solutions for unbiased readout of EV biomarker studies and routine clinical sampling and diagnostics providing the input for design of larger validation studies employing urine EVs as biomarkers for particular conditions and diseases.
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Affiliation(s)
- Riccardo Vago
- grid.18887.3e0000000417581884Urological Research Institute, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy ,grid.15496.3f0000 0001 0439 0892Università Vita-Salute San Raffaele, 20132 Milan, Italy
| | | | | | - Natasa Zarovni
- Exosomics S.p.A, 53100 Siena, Italy ,HansaBiomed Life Sciences OU, Tallinn, Estonia
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Gryp T, Vanholder R, Glorieux G. The authors reply. Kidney Int 2020; 98:784. [PMID: 32828239 DOI: 10.1016/j.kint.2020.05.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 05/07/2020] [Indexed: 11/16/2022]
Affiliation(s)
- Tessa Gryp
- Department of Internal Medicine and Pediatrics, Nephrology Division, Ghent University Hospital, Ghent, Belgium
| | - Raymond Vanholder
- Department of Internal Medicine and Pediatrics, Nephrology Division, Ghent University Hospital, Ghent, Belgium
| | - Griet Glorieux
- Department of Internal Medicine and Pediatrics, Nephrology Division, Ghent University Hospital, Ghent, Belgium.
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