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Role and Efficacy of Current Biomarkers in Bladder Cancer
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Role and Efficacy of Current Biomarkers in Bladder Cancer

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 7446

Special Issue Editors

Prof. Dr. Michael Rink

E-Mail
Guest Editor
Dept. of Urology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg, Germany
Interests: urologic oncology; urothelial carcinoma; renal cell carcinoma; translational and outcome research; biomarkers
Dr. Armin Soave

E-Mail Website
Co-Guest Editor
Department of Urology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany
Interests: andrology; sexual medicine; male sexual dysfunction; reconstructive urology; genitourinary reconstruction; gender affirmation surgery

Special Issue Information

Dear Colleagues,

Urothelial carcinoma of the bladder (UBC) is a common urological malignancy with standardized treatment paradigms for non-muscle invasive and muscle-invasive disease. However, UCB is a clinically and genetically highly heterogeneous disease. Genome-wide association studies have demonstrated the importance of genetics, and several susceptibility loci associated with the risk of UBC seem to be important drivers for disease outcomes. Over the past decade, seminal investigations have provided tremendous novel insights into UBC biology. Of foremost significance, phenotypically similar tumors may harbor completely different molecular genotypes, representing the individuality of each tumor and its host. Differences in the molecular landscape of individual tumors probably explain, to some extent, the potential lack and variability of efficacy in local treatments as well as systemic and targeted therapies. Biomarkers represent an elegant but challenging approach to reflecting individual tumor biology and offer great potential for the improvement of UBC treatment.

In this Special Issue, we invite manuscripts dealing with new research findings and advances in blood-based, urine or tissue biomarkers in bladder cancer. Since urothelial carcinoma of the upper urinary tract (UTUC) is associated with bladder cancer development as well as intravesical recurrences, articles on UTUC biomarkers investigating bladder cancer incidence or recurrence are also invited. Both original research and review articles are warmly welcomed. Reviews should provide an up-to-date overview of the current state of the art and critically discuss the current clinical implications as well as future perspectives of UCB tumor biology and biomarkers. Potential topics include but are not limited to the following:

  • The reflection of intra- and interindividual tumor heterogeneity;
  • The association of biomarkers with UCB tumor biology and aggressiveness;
  • The association of UCB biomarkers with disease recurrence or outcomes;
  • The immune environment and/or microenvironment at tumor sites and/or at a systemic level;
  • Circulating blood-based or urine biomarkers predictive for therapy response and treatment monitoring;
  • Marker-based decision making for multimodal treatment approaches.

Please feel free to contact us and send us any suggestions that you would like to discuss beforehand. We look forward to and welcome your participation in this Special Issue.

Prof. Dr. Michael Rink
Guest Editor
Dr. Armin Soave
Co-Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bladder cancer
  • urothelial carcinoma
  • biomarker
  • tumor biology
  • circulating tumor cells
  • TURBT
  • radical cystectomy
  • chemotherapy and immunotherapy
  • targeted therapy

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Published Papers (3 papers)

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Research

7 pages, 907 KiB  
Communication
HUS1 as a Potential Therapeutic Target in Urothelial Cancer
by Andrea Katharina Lindner, Tobias Furlan, Jacob J. Orme, Gennadi Tulchiner, Nina Staudacher, David D’Andrea, Zoran Culig and Renate Pichler
J. Clin. Med. 2022, 11(8), 2208; https://doi.org/10.3390/jcm11082208 - 15 Apr 2022
Viewed by 2116
Abstract
Platinum-based chemotherapy is the standard of care with concern to first-line systemic therapy for metastatic disease in urothelial cancer (UC). Resistance to chemotherapy despite an initial response is linked with the ability to remove platinum-based DNA adducts and to repair chemotherapy-induced DNA lesions [...] Read more.
Platinum-based chemotherapy is the standard of care with concern to first-line systemic therapy for metastatic disease in urothelial cancer (UC). Resistance to chemotherapy despite an initial response is linked with the ability to remove platinum-based DNA adducts and to repair chemotherapy-induced DNA lesions by various DNA repair proteins. The Rad9-Rad1-HUS1 complex that is loaded onto DNA at sites of damage is involved in checkpoint activation as well as DNA repair. Here, we addressed for the first time the potential influence of HUS1 expression in urothelial carcinogenesis (using two human basal urothelial cancer cell lines UM-UC-3 and HT1197) and its role as a potential therapeutic target for predicting responses to platinum-based chemotherapy. Specific inhibition of HUS1 expression in both cell lines was achieved by specific siRNA and validated by Western blot. In order to define the possible importance of HUS1 in the regulation of cellular proliferation, parental and resistant cells were treated with increasing concentrations of either control or HUS1 siRNA. HUS1 protein expression was observed in both human basal urothelial cancer cell lines UM-UC-3 and HT1197. In cisplatin-sensitive cells, knock-down of HUS1 inhibited cellular proliferation in the presence of cisplatin. On the contrary, knock-down of HUS1 in resistant cells did not result in a re-sensitization to cisplatin. Finally, RNAseq data from the Cancer Genome Atlas provided evidence that HUS1 expression is a significant prognostic factor for poor survival in UC patients. In summary, HUS1 may acts as an oncogene in UC and might be a key determinant of the cellular response to cisplatin-based chemotherapy. Full article
(This article belongs to the Special Issue Role and Efficacy of Current Biomarkers in Bladder Cancer)
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13 pages, 2533 KiB  
Article
Prognostic Impact of CD36 Immunohistochemical Expression in Patients with Muscle-Invasive Bladder Cancer Treated with Cystectomy and Adjuvant Chemotherapy
by Juan Carlos Pardo, Tamara Sanhueza, Vicenç Ruiz de Porras, Olatz Etxaniz, Helena Rodriguez, Anna Martinez-Cardús, Enrique Grande, Daniel Castellano, Miquel A. Climent, Tania Lobato, Lidia Estudillo, Mireia Jordà, Cristina Carrato and Albert Font
J. Clin. Med. 2022, 11(3), 497; https://doi.org/10.3390/jcm11030497 - 19 Jan 2022
Cited by 7 | Viewed by 2243
Abstract
Neoadjuvant chemotherapy followed by a cystectomy is the standard treatment in muscle-invasive bladder cancer (MIBC). However, the role of chemotherapy in the adjuvant setting remains controversial, and therefore new prognostic and predictive biomarkers are needed to improve the selection of MIBC patients. While [...] Read more.
Neoadjuvant chemotherapy followed by a cystectomy is the standard treatment in muscle-invasive bladder cancer (MIBC). However, the role of chemotherapy in the adjuvant setting remains controversial, and therefore new prognostic and predictive biomarkers are needed to improve the selection of MIBC patients. While lipid metabolism has been related to several biological processes in many tumours, including bladder cancer, no metabolic biomarkers have been identified as prognostic in routine clinical practice. In this multicentre, retrospective study of 198 patients treated with cystectomy followed by platinum-based adjuvant chemotherapy, we analysed the immunohistochemical expression of CD36 and correlated our findings with clinicopathological characteristics and survival. CD36 immunostaining was positive in 30 patients (15%) and associated with more advanced pathologic stages (pT3b-T4; p = 0.015). Moreover, a trend toward lymph node involvement in CD36-positive tumours, especially in earlier disease stages (pT1-T3; p = 0.101), was also observed. Among patients with tumour progression during the first 12 months after cystectomy, disease-free survival was shorter in CD36-positive tumours than in those CD36-negative (6.51 months (95% CI 5.05–7.96) vs. 8.74 months (95% CI 8.16–9.32); p = 0.049). Our results suggest an association between CD36 immunopositivity and more aggressive features of MIBC and lead us to suggest that CD36 could well be a useful prognostic marker in MIBC. Full article
(This article belongs to the Special Issue Role and Efficacy of Current Biomarkers in Bladder Cancer)
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12 pages, 13695 KiB  
Article
Enhanced Expression but Decreased Specific Activity of Matrix Metalloproteinase 10 (MMP-10) in Comparison with Matrix Metalloproteinase 3 (MMP-3) in Human Urinary Bladder Carcinoma
by Jacek Kudelski, Grzegorz Młynarczyk, Monika Gudowska-Sawczuk, Barbara Mroczko, Barbara Darewicz, Marta Bruczko-Goralewska, Krzysztof Sobolewski and Lech Romanowicz
J. Clin. Med. 2021, 10(16), 3683; https://doi.org/10.3390/jcm10163683 - 19 Aug 2021
Cited by 7 | Viewed by 2100
Abstract
Human urinary bladder cancer is a huge worldwide oncological problem causing many deaths every year. The degradation of extracellular matrix (ECM) induced by molecules such as matrix metalloproteinases (MMPs) is one of the main factors influencing the process of metastasis origination. The MMP [...] Read more.
Human urinary bladder cancer is a huge worldwide oncological problem causing many deaths every year. The degradation of extracellular matrix (ECM) induced by molecules such as matrix metalloproteinases (MMPs) is one of the main factors influencing the process of metastasis origination. The MMP expression is tied to tumor aggressiveness, stage, and patient prognosis. The cleavage of constituent proteins is initiated and prolonged by matrix metalloproteinases, such as MMP-3 and MMP-10. The aim of this study was to evaluate the expression and activity of both MMPs in human urinary bladder cancer occurring at various stages of the disease. Tissue samples from patients with urinary bladder cancer were analyzed. Samples were collected from patients with a low- and high-grade cancer. Control tissue was collected from the site opposite to the tumor. DNA content, MMPs content, and activity of MMP-3 and MMP-10 were measured using ELISA and Western blot techniques. MMP-3 and MMP-10 occur in high molecular complexes in human urinary bladder in healthy and cancerous tissues. Particularly, in high-grade tumors, the content of MMP-10 prevails over MMP-3. The actual and specific activities vary in both grades of urinary bladder cancer; however, the highest activity for MMP-3 and MMP-10 was found in low-grade tissues. In conclusion, MMP-10 had a higher content, but a lower activity in all investigated tissues compared to MMP-3. Generally, obtained results demonstrated a contrary participation of MMP-3 and MMP-10 in ECM remodeling what may be crucial in the pathogenesis of human urinary bladder carcinoma. Full article
(This article belongs to the Special Issue Role and Efficacy of Current Biomarkers in Bladder Cancer)
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