Biomarkers of Urological Disease

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 15916

Special Issue Editors

Department of Urology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
Interests: urology; cancer; biomarker
Biological Mass Spectrometry and Translational Proteomics Laboratory, Chang Gung University, Taoyuan 333, Taiwan
Interests: proteomics; metabolomics; disease biomarkers; biological mass spectrometry; analytical chemistry

Special Issue Information

Dear Colleagues,

Diagnosis is the benchmark of disease control and treatment. A good biomarker may be a surrogate for disease status and play a pivotal role in many diseases, including cancers. In the urological field, prostate-specific antigen (PSA) is a game-changing biomarker for prostate cancer. It changed the landscape of diagnosis, treatment outcome, recurrence, and long-term prognosis of prostate cancer. However, bladder cancer is one of the major cancers without a reliable tumor marker. As the bladder is the reservoir of urine, biomarkers for urothelial cancer detected from urine could stand on a good rationale. Recent -omics studies have focused on this field. Most kidney cancers are silent in the early stage, and incidentaloma could be a tremendous challenge to patient survival.

In this Special Issue, we welcome any research that sheds light on the advancement of our understanding of diseases in the urological field. Papers on the following are especially welcome:

  1. Biomarkers in all urological diseases, including cancer;
  2. Review of present biomarkers: where we stand and future perspectives (solicited or unsolicited);
  3. Liquid biopsy (circulating tumor cells, cell-free DNA): as predictive biomarkers in metastatic diseases;
  4. Theranostics.

Prof. Dr. Chien Lun Chen
Prof. Yi-Ting Chen
Guest Editors

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Keywords

  • biomarker
  • bladder
  • prostate
  • kidney
  • cancer

Published Papers (10 papers)

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16 pages, 2471 KiB  
Article
Urinary Metabolomic Analysis of Prostate Cancer by UPLC-FTMS and UPLC-Ion Trap MSn
by Chien-Lun Chen, Yi-Ting Chen, Wen-Yu Liao, Yu-Sun Chang, Jau-Song Yu and Bao-Rong Juo
Diagnostics 2023, 13(13), 2270; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13132270 - 04 Jul 2023
Viewed by 797
Abstract
Accumulative evidence suggests metabolic disorders correlate with prostate cancer. Metabolic profiling of urine allows the measurement of numerous metabolites simultaneously. This study set up a metabolomic platform consisting of UPLC-FTMS and UPLC-ion trap MSn for urine metabolome analysis. The platform improved retention [...] Read more.
Accumulative evidence suggests metabolic disorders correlate with prostate cancer. Metabolic profiling of urine allows the measurement of numerous metabolites simultaneously. This study set up a metabolomic platform consisting of UPLC-FTMS and UPLC-ion trap MSn for urine metabolome analysis. The platform improved retention time, mass accuracy, and signal stability. Additionally, the product ion spectrum obtained from ion trap MSn facilitated structure elucidation of candidate metabolites, especially when authentic standards were not available. Urine samples from six hernia patients and six BPH patients were used for the initial establishment of the analytic platform. This platform was further employed to analyze the urine samples of 27 PCa and 49 BPH patients. Choosing the upper and lower 16% of metabolites, 258 metabolite candidates were selected. Twenty-four of them with AUC values larger than 0.65 were further selected. Eighteen of the twenty-four features can be matched in METLIN and HMDB. Eleven of the eighteen features can be interpreted by MSn experiments. They were used for the combination achieving the best differential power. Finally, four metabolites were combined to reach the AUC value of 0.842 (CI 95, 0.7559 to 0.9279). This study demonstrates the urinary metabolomic analysis of prostate cancer and sheds light on future research. Full article
(This article belongs to the Special Issue Biomarkers of Urological Disease)
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12 pages, 1006 KiB  
Article
Association between the Immunophenotype of Peripheral Blood from mCRPC Patients and the Outcomes of Radium-223 Treatment
by Elisabet Cantó, Georgia Anguera, Natalia Jiménez, Begoña Mellado, Ona Ramírez, Anais Mariscal, Pablo Maroto and Silvia Vidal
Diagnostics 2023, 13(13), 2222; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13132222 - 29 Jun 2023
Viewed by 1083
Abstract
(1) Background: Prostate cancer is the second most common cancer in men, with androgen suppression as the standard treatment. Despite initially responding to castration, most metastatic prostate cancer patients eventually experience progression. In these cases, Radium-223 is the chosen treatment. We hypothesized that [...] Read more.
(1) Background: Prostate cancer is the second most common cancer in men, with androgen suppression as the standard treatment. Despite initially responding to castration, most metastatic prostate cancer patients eventually experience progression. In these cases, Radium-223 is the chosen treatment. We hypothesized that the immunophenotype of circulating leukocytes conditions the response to Radium-223 treatment. (2) Material and Methods: In this prospective study, we collected peripheral blood from twelve mCRPC patients and nine healthy donors before (baseline) and during treatment with Radium-223. Immunophenotyping and the percentages of leukocyte–platelet complexes were determined by flow cytometry. The increments or decrements of leukocyte subsets between the baseline and the second Radium-223 injection were also calculated. (3) Results: At baseline, the mCRPC patients had a lower percentages of CD4+ T cells and B cells and higher percentages of NK and neutrophils than the HDs. In addition, they had more OX40+ CD4+ T cells, PD-L1+ CD8low cells, PD-L1+ B cells, PD-L1+ NK cells, and monocyte–platelet complexes than the HDs. Moreover, patients with slow and fast progression had different percentages of PD-L1+ CD8+ T cells. In particular, slow progression patients underwent an increment of PD-L1+ CD8+ T cells after two cycles of Radium-223. (4) Conclusions: The characterization of circulating immune cells before initiating Radium-223 treatment could become a non-invasive indicator of the response. Full article
(This article belongs to the Special Issue Biomarkers of Urological Disease)
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11 pages, 919 KiB  
Article
Differential Expression of LncRNA in Bladder Cancer Development
by Lorenzo Spirito, Rufina Maturi, Sara Carmela Credendino, Celeste Manfredi, Davide Arcaniolo, Marco De Martino, Francesco Esposito, Luigi Napolitano, Francesco Di Bello, Alfredo Fusco, Pierlorenzo Pallante, Marco De Sio and Gabriella De Vita
Diagnostics 2023, 13(10), 1745; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13101745 - 15 May 2023
Cited by 4 | Viewed by 1096
Abstract
Bladder cancer (BC) is the tenth most common cancer, with urothelial carcinoma representing about 90% of all BC, including neoplasms and carcinomas of different grades of malignancy. Urinary cytology has a significant role in BC screening and surveillance, although it has a low [...] Read more.
Bladder cancer (BC) is the tenth most common cancer, with urothelial carcinoma representing about 90% of all BC, including neoplasms and carcinomas of different grades of malignancy. Urinary cytology has a significant role in BC screening and surveillance, although it has a low detection rate and high dependence on the pathologist’s experience. The currently available biomarkers are not implemented into routine clinical practice due to high costs or low sensitivity. In recent years, the role of lncRNAs in BC has emerged, even though it is still poorly explored. We have previously shown that the lncRNAs Metallophosphoesterase Domain-Containing 2 Antisense RNA 1 (MPPED2-AS1), Rhabdomyosarcoma-2 Associated Transcript (RMST), Kelch-like protein 14 antisense (Klhl14AS) and Prader Willi/Angelman region RNA 5 (PAR5) are involved in the progression of different types of cancers. Here, we investigated the expression of these molecules in BC, first by interrogating the GEPIA database and observing a different distribution of expression levels between normal and cancer specimens. We then measured them in a cohort of neoplastic bladder lesions, either benign or malignant, from patients with suspicion of BC undergoing transurethral resection of bladder tumor (TURBT). The total RNA from biopsies was analyzed using qRT-PCR for the expression of the four lncRNA genes, showing differential expression of the investigated lncRNAs between normal tissue, benign lesions and cancers. In conclusion, the data reported here highlight the involvement of novel lncRNAs in BC development, whose altered expression could potentially affect the regulatory circuits in which these molecules are involved. Our study paves the way for testing lncRNA genes as markers for BC diagnosis and/or follow-up. Full article
(This article belongs to the Special Issue Biomarkers of Urological Disease)
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12 pages, 1176 KiB  
Article
Circulating Tumor Cells Predict Response of Neoadjuvant Chemotherapy in Patients with Bladder Cancer: A Preliminary Study
by Yu-Cing Jhuo, Tai-Lung Cha, Chien-Chang Kao, Yi-Ta Tsai, Sheng-Tang Wu, En Meng, Chih-Wei Tsao, Chin-Li Chen, Hui-Kung Ting, Guang-Huan Sun, Dah-Shyong Yu, Sun-Yran Chang and Ming-Hsin Yang
Diagnostics 2023, 13(6), 1032; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13061032 - 08 Mar 2023
Viewed by 1547
Abstract
This study aimed to explore the existence of circulating tumor cells (CTCs) in patients with muscle-invasive bladder cancer (MIBC) and their predictive potential for response to neoadjuvant chemotherapy (NAC). From 33 blood samples of MIBC patients, CTCs were isolated by cell surface markers [...] Read more.
This study aimed to explore the existence of circulating tumor cells (CTCs) in patients with muscle-invasive bladder cancer (MIBC) and their predictive potential for response to neoadjuvant chemotherapy (NAC). From 33 blood samples of MIBC patients, CTCs were isolated by cell surface markers and enriched by the IsoFlux™ device, followed by morphological and immunofluorescent identification. CTCs were detected at baseline in all samples. Immunofluorescence confirmed the tumor origin. MIBC patients were stratified by NAC response into the disease control (DC) and progressive disease (PD) groups. In the DC group, the number of CTCs decreased significantly after four courses of NAC (p < 0.0001). CTC counts in 7.5 mL after four NAC cycles were highly correlated with postoperative pathological T stage (p < 0.0001). Our study demonstrated that CTCs might represent a valuable predictive marker for NAC response in MIBC. CTC detection in MIBC patients could allow early arrangement of radical cystectomy for NAC non-responders to prevent disease progression while receiving the NAC courses. Full article
(This article belongs to the Special Issue Biomarkers of Urological Disease)
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12 pages, 2254 KiB  
Article
Simple and Convenient Method for Assessing the Severity of Bleeding during Endoscopic Prostate Surgery and the Relationships between Its Corresponding Surgical Outcomes
by Shu-Chuan Weng, Shu-Han Tsao, Han-Yu Tsai, Horng-Heng Juang, Yu-Hsiang Lin, Phei-Lang Chang, Chien-Lun Chen and Chen-Pang Hou
Diagnostics 2023, 13(4), 592; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics13040592 - 06 Feb 2023
Viewed by 1230
Abstract
Bleeding during endoscopic prostate surgery is often overlooked, and appropriate measurement techniques are rarely applied. We proposed a simple and convenient method for assessing the severity of bleeding during endoscopic prostate surgery. We determined the factors affecting bleeding severity and whether they affected [...] Read more.
Bleeding during endoscopic prostate surgery is often overlooked, and appropriate measurement techniques are rarely applied. We proposed a simple and convenient method for assessing the severity of bleeding during endoscopic prostate surgery. We determined the factors affecting bleeding severity and whether they affected the surgical results and functional outcomes. Records from March 2019 to April 2022 were obtained for selected patients who underwent endoscopic prostate enucleation through either 120-W Vela XL Thulium:YAG laser or bipolar plasma enucleation of the prostate. The bleeding index was measured using the following equation: irrigant hemoglobin (Hb) concentration (g/dL) × irrigation fluid volume (mL)/preoperative blood Hb concentration (g/dL) × enucleated tissue (g). Our research revealed that patients who underwent surgery employing the thulium laser, those aged over 80 years, and those with a preoperative maximal flow rate (Qmax) of more than 10 cc/s experienced less surgical bleeding. The patients’ treatment outcomes differed depending on the severity of the bleeding. Enucleating prostate tissue was easier in the patients with less severe bleeding, who also had a lower risk of developing urinary tract infections and an improved Qmax. Full article
(This article belongs to the Special Issue Biomarkers of Urological Disease)
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21 pages, 4311 KiB  
Article
CBX Family Members in Two Major Subtypes of Renal Cell Carcinoma: A Comparative Bioinformatic Analysis
by Anna Maria Grimaldi, Ornella Affinito, Marco Salvatore and Monica Franzese
Diagnostics 2022, 12(10), 2452; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12102452 - 11 Oct 2022
Cited by 3 | Viewed by 1378
Abstract
The biological function and clinical values of Chromobox (CBX) family proteins in renal cell carcinoma (RCC) are still poorly investigated. This study aimed to compare the expression profiles and clinical relevance of CBXs between the two most frequent subtypes of RCC, clear cell [...] Read more.
The biological function and clinical values of Chromobox (CBX) family proteins in renal cell carcinoma (RCC) are still poorly investigated. This study aimed to compare the expression profiles and clinical relevance of CBXs between the two most frequent subtypes of RCC, clear cell renal cell carcinomas (ccRCC) and papillary renal cell carcinomas (pRCC), and to investigate whether CBXs would play a more or less similar role in the pathogenesis and progression of these RCC subtypes. Considering these two RCC populations in the TCGA database, we built a bioinformatics framework by integrating a computational pipeline with several online tools. CBXs showed a similar trend in ccRCC and pRCC tissues but with some features specific for each subtype. Specifically, the relative expressions of CBX3 and CBX2 were, respectively, the highest and lowest among all CBXs in both RCC subtypes. These data also found confirmation in cellular validation. Except for CBX4 and CBX8, all others were deregulated in the ccRCC subtype. CBX1, CBX6, and CBX7 were also significantly associated with the tumor stage. Further, low expression levels of CBX1, CBX5, CBX6, CBX7, and high expression of CBX8 were associated with poor prognosis. Otherwise, in the pRCC subtype, CBX2, CBX3, CBX7, and CBX8 were deregulated, and CBX2, CBX6, and CBX7 were associated with the tumor stage. In addition, in pRCC patients, low expression levels of CBX2, CBX4, and CBX7 were associated with an unfavorable prognosis. Similarly, CBX3, CBX6, and CBX7 presented the highest alteration rate in both subtypes and were found to be functionally related to histone binding, nuclear chromosomes, and heterochromatin. Furthermore, CBX gene expression levels correlated with immune cell infiltration, suggesting that CBXs might reflect the immune status of RCC subtypes. Our results highlight similarities and differences of CBXs within the two major RCC subtypes, providing new insights for future eligible biomarkers or possible molecular therapeutic targets for these diseases. Full article
(This article belongs to the Special Issue Biomarkers of Urological Disease)
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16 pages, 5156 KiB  
Article
Strategies for Isolating and Propagating Circulating Tumor Cells in Men with Metastatic Prostate Cancer
by Gerit Theil, Joanna Bialek, Christine Weiß, Felix Lindner and Paolo Fornara
Diagnostics 2022, 12(2), 497; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12020497 - 15 Feb 2022
Cited by 2 | Viewed by 2134
Abstract
Selecting a well-suited method for isolating/characterizing circulating tumor cells (CTCs) is challenging. Evaluating sensitive and specific markers for prostate cancer (PCa)-specific CTC identification and analysis is crucial. We used the CellCollector EpCAM-functionalized system (CC-EpCAM) and evaluated and developed a PCa-functionalized version (CC-PCa); we [...] Read more.
Selecting a well-suited method for isolating/characterizing circulating tumor cells (CTCs) is challenging. Evaluating sensitive and specific markers for prostate cancer (PCa)-specific CTC identification and analysis is crucial. We used the CellCollector EpCAM-functionalized system (CC-EpCAM) and evaluated and developed a PCa-functionalized version (CC-PCa); we then compared CTC isolation techniques that exploit the physical and biological properties of CTCs. We established two cohorts of metastatic PCa patients (mPCa; 15 in cohort 1 and 10 in cohort 2). CTC cultivation experiments were conducted with two capturing methods (Ficoll and ScreenCell). The most sensitive detection rates and highest CTC counts were reached with the CC-PCa and ScreenCell system. Patients with ≥5 CTCs isolated with CC-EpCAM had an overall survival (OS) of 0.93 years, and patients with ≥5 CTCs isolated with CC-PCa had an OS of 1.5 years in cohort 1. Nevertheless, we observed the highest sensitivity and specificity for 24-month survival by the Ficoll with CD45 depletion and ScreenCell system with May-Grunwald Giemsa (MGG) staining. The EpCAM molecule is an essential factor related to OS for CTC isolation based on biological properties in mPCa patients. The best-suited CTC capture system is not limited to one characteristic of cells but adapted to downstream analysis. Full article
(This article belongs to the Special Issue Biomarkers of Urological Disease)
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13 pages, 902 KiB  
Article
Dynamic Echocardiographic Assessments Reveal Septal E/e’ Ratio as Independent Predictor of Intradialytic Hypotension in Maintenance for Hemodialysis Patients with Preserved Ejection Fraction
by Chun-Yu Chen, Ning-I Yang, Chin-Chan Lee, Ming-Jui Hung, Wen-Jin Cherng, Heng-Jung Hsu, Chiao-Yin Sun and I-Wen Wu
Diagnostics 2021, 11(12), 2266; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11122266 - 03 Dec 2021
Cited by 1 | Viewed by 1299
Abstract
Background: Intradialytic hypotension (IDH) is a frequent and grave complication of hemodialysis (HD). However, the dynamic hemodynamic changes and cardiac performances during each dialytic session have been rarely explored in patients having IDH. Methods: Seventy-six HD patients (IDH = 40, controls = 36) [...] Read more.
Background: Intradialytic hypotension (IDH) is a frequent and grave complication of hemodialysis (HD). However, the dynamic hemodynamic changes and cardiac performances during each dialytic session have been rarely explored in patients having IDH. Methods: Seventy-six HD patients (IDH = 40, controls = 36) were enrolled. Echocardiography examinations were performed in all patients at the pre-HD, during-HD and post-HD phases of a single HD session. A two-way analysis of variance was applied to compare differences of echocardiographic parameters between IDH and controls over time. The risk association was estimated by using a logistic regression analysis. Results: The IDH patients had a higher ejection fraction during HD followed by a greater reduction at the post-HD phase than the controls. Significant decreases in septal ratios of transmitral flow velocity to annular velocity (E/e’) over times were detected between IDH patients and controls after adjusting for gender, age and ultrafiltration (p = 0.016). A lower septal E/e’ ratio was independently associated with IDH (OR = 0.040; 95% CI = 0.003–0.606; p = 0.02). In contrast, significant systolic and diastolic dysfunctions over time were found in diabetic IDH compared to non-diabetic counterparts. Conclusion: The septal E/e’ ratio was a significant predictor for IDH. Full article
(This article belongs to the Special Issue Biomarkers of Urological Disease)
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12 pages, 1249 KiB  
Article
Identification of piRNA Targets in Urinary Extracellular Vesicles for the Diagnosis of Prostate Cancer
by Qiang Peng, Peter Ka-Fung Chiu, Christine Yim-Ping Wong, Carol Ka-Lo Cheng, Jeremy Yuen-Chun Teoh and Chi-Fai Ng
Diagnostics 2021, 11(10), 1828; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11101828 - 03 Oct 2021
Cited by 20 | Viewed by 2211
Abstract
Emerging studies demonstrate that PIWI-interacting RNAs (piRNAs) are associated with various human cancers. This study aimed to evaluate the urinary extracellular vesicles (EVs) piRNAs as non-invasive biomarkers for prostate cancer (PCa) diagnosis. RNA was extracted from urinary EVs from five PCa patients and [...] Read more.
Emerging studies demonstrate that PIWI-interacting RNAs (piRNAs) are associated with various human cancers. This study aimed to evaluate the urinary extracellular vesicles (EVs) piRNAs as non-invasive biomarkers for prostate cancer (PCa) diagnosis. RNA was extracted from urinary EVs from five PCa patients and five healthy controls (HC), and the piRNAs were analyzed by small RNA sequencing. Dysregulated piRNAs were identified and then validated in another 30 PCa patients and 10 HC by reverse-transcription polymerase chain reaction (RT-qPCR). The expressions of novel_pir349843, novel_pir382289, novel_pir158533, and hsa_piR_002468 in urinary EVs were significantly increased in the PCa group compared with the HC group. The area under the curve (AUC) of novel_pir158533, novel_pir349843, novel_pir382289, hsa_piR_002468, and the combination of the four piRNA in PCa diagnosis was 0.723, 0.757, 0.777, 0.783, and 0.853, respectively. After the RNAhybrid program analysis, all four piRNAs had multiple potential binding sites with key mRNAs in PTEN/PI3K/Akt, Wnt/beta-catenin, or androgen receptor pathway, which are critical in PCa development and progression. In conclusion, our findings indicate that specific piRNAs in urinary EVs may serve as non-invasive diagnostic biomarkers for PCa. Full article
(This article belongs to the Special Issue Biomarkers of Urological Disease)
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18 pages, 1961 KiB  
Systematic Review
Potential Value of Visfatin, Omentin-1, Nesfatin-1 and Apelin in Renal Cell Carcinoma (RCC): A Systematic Review and Meta-Analysis
by Sugania Malar Chinapayan, Shanggar Kuppusamy, Ning Yi Yap, Komathi Perumal, Glenda Gobe and Retnagowri Rajandram
Diagnostics 2022, 12(12), 3069; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12123069 - 06 Dec 2022
Cited by 2 | Viewed by 1138
Abstract
Renal cell carcinoma (RCC) is the most lethal genitourinary malignancy. Obesity is a risk factor for RCC development. The role of adipokines in the relationship between obesity and RCC requires confirmatory evidence in the form of a systematic review and meta-analysis, specifically for [...] Read more.
Renal cell carcinoma (RCC) is the most lethal genitourinary malignancy. Obesity is a risk factor for RCC development. The role of adipokines in the relationship between obesity and RCC requires confirmatory evidence in the form of a systematic review and meta-analysis, specifically for visfatin, omentin-1, nesfatin-1 and apelin. A search of databases up to July 2022 (PubMed, Web of Science and Scopus) for studies reporting the association of these selected adipokines with RCC was conducted. A total of 13 studies fulfilled the selection criteria. Only visfatin (p < 0.05) and nesfatin-1 (p < 0.05) had a significant association with RCC. Meanwhile, apelin and omentin-1 showed no association with RCC. The meta-analysis results of nesfatin-1 showed no association with early-stage (OR = 0.09, 95% CI = −0.12–0.29, p = 0.41), late-stage (OR = 0.36, 95% CI = 0.07–1.89, p = 0.23) and low-grade (OR = 1.75, 95% CI = 0.37–8.27, p = 0.48) RCC. However, nesfatin-1 showed an association with a high grade of the disease (OR = 0.29, 95% CI = 0.13–0.61, p = 0.001) and poorer overall survival (OS) (HR = 3.86, 95% CI = 2.18–6.85; p < 0.01). Apelin showed no association with the risk of RCC development (mean difference = 21.15, 95% CI = −23.69–65.99, p = 0.36) and OS (HR = 1.04, 95% Cl = 0.45–2.41; p = 0.92). Although the number of studies evaluated was limited, analysis from this systematic review and meta-analysis indicate that visfatin and nesfatin-1 were elevated. In summary, these adipokines may play a role in the development and progression of RCC and hence may have potential diagnostic and prognostic capabilities for RCC. Full article
(This article belongs to the Special Issue Biomarkers of Urological Disease)
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