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Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2018) | Viewed by 64890

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Special Issue Editors

Assoc. Prof. Dr. Thorsten Ecke

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Guest Editor

Department of Urology, HELIOS Hospital Bad Saarow, Bad Saarow, Germany
Interests: bladder cancer; prostate cancer; urologic oncology; molecular biology; tumor markers; diagnostics; biomarkers in urological malignancies
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Thomas Otto

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Guest Editor

Department of Urology, Lukas Hospital Neuss, D-41464 Neuss, Germany
Interests: endourology; bladder cancer; urologic oncology; molecular biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bladder cancer is the most common cancer of the urinary tract and ranks fifth among cancers in men in Western countries. Early diagnosis of bladder cancer is mainly based on cystoscopy after gross hematuria. Based on urine or urinary cells, only a few molecular markers have been approved by the Federal Food and Drug Administration (FDA) so far. Urine soluble markers should be able to ensure primary diagnosis, follow-up control and screening of high-risk populations. In addition, these markers are designated merely as supporting tools for monitoring bladder cancer patients instead of replacing cystoscopy. New biomarkers in serum and urine including nucleic acid or protein-based tissue biomarkers have been described. However, not only the diagnosis, but also the prognosis or further prediction of this very common disease is important to know. To say it in Arthur Rimbaud’s words, the vision of new scientific reports should be illuminated in this Special Issue with focus on “Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer—Illumination of a Vision”.

We warmly welcome submissions, including original papers and reviews, on this widely-discussed topic.

Assoc. Prof. Dr. Thorsten Ecke
Prof. Dr. Thomas Otto
Guest Editors

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

urinary biomarkers on bladder cancer
serum/plasma biomarkers
tissue biomarkers (nuleic acid/protein-based)
epigenetic markers
prognostic factors
predictive factors
multivariate models

Related Special Issue

Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision 2.0 in International Journal of Molecular Sciences (14 articles)

Published Papers (13 papers)

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Editorial

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Illumination of a Vision—How Arthur Rimbaud Will Give Us Motivation to Find New Input into Bladder Cancer Biomarker Research

by Thorsten H. Ecke and Thomas Otto

Int. J. Mol. Sci. 2017, 18(11), 2463; https://doi.org/10.3390/ijms18112463 - 19 Nov 2017

Cited by 2 | Viewed by 3464

Abstract

Bladder cancer (BC) accounts for approximately 430,000 new cases and 165,000 deaths each year worldwide [...] Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

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Research

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12 pages, 1267 KiB

Open AccessArticle

UBC^® Rapid Test—A Urinary Point-of-Care (POC) Assay for Diagnosis of Bladder Cancer with a focus on Non-Muscle Invasive High-Grade Tumors: Results of a Multicenter-Study

by Thorsten H. Ecke, Sarah Weiß, Carsten Stephan, Steffen Hallmann, Christian Arndt, Dimitri Barski, Thomas Otto and Holger Gerullis

Int. J. Mol. Sci. 2018, 19(12), 3841; https://doi.org/10.3390/ijms19123841 - 02 Dec 2018

Cited by 21 | Viewed by 4566

Abstract

Objectives: UBC^® Rapid Test measures soluble fragments of cytokeratins 8 and 18 in urine. We present results of a multicenter study using an updated version of UBC^® Rapid Test in bladder cancer patients, patients with urinary bladder cancer positive history, and healthy controls. Material and Methods: In total 530 urine samples have been included in this study. Clinical urine samples were used from 242 patients with tumors of the urinary bladder (134 non-muscle-invasive low-grade tumors (NMI-LG), 48 non-muscle-invasive high-grade tumors (NMI-HG), and 60 muscle-invasive high-grade tumors (MI-HG)), 62 patients with non-evidence of disease (NED), and 226 healthy controls. Urine samples were analyzed by the UBC^® Rapid point-of-care (POC) assay and evaluated by Concile Omega 100 POC Reader. All statistical analyses have been performed using R version 3.2.3. Results: Elevated levels of UBC^® Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p < 0.001). The sensitivity for the whole bladder cancer cohort was 53.3% (positive predictive value (PPV) 90.2%, negative predictive value (NPV) 65.2%) and was 38.8% (PPV 78.8%, NPV 72.1%) for non-muscle-invasive low-grade bladder cancer; 75.0% (PPV 72.0%, NPV 94.7%) for non-muscle-invasive high-grade bladder cancer and 68.3% (PPV 74.6%, NPV 91.8%) for muscle-invasive high-grade bladder cancer. The specificity for the statistical calculations was 93.8%. The cut-off value (10 µg/L) was evaluated for the whole patient cohort. The area under the curve of the quantitative UBC^® Rapid Test using the optimal threshold obtained by receiver operating characteristics (ROC) analysis was 0.774. Elevated values of UBC^® Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumors and the healthy control group. Conclusions: UBC^® Rapid Test has potential to be a clinically valuable urinary protein biomarker for detection of high-grade bladder cancer patients and could be added in the management of NMI-HG tumors. UBC^® Rapid results generated in both study centers in the present multicenter study are very similar and reproducible. Furthermore UBC^® Rapid Test is standardized and calibrated and thus independent of used batch of test as well as study site. Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

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14 pages, 1369 KiB

Open AccessArticle

mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants

by Markus Eckstein, Ralph Markus Wirtz, Matthias Gross-Weege, Johannes Breyer, Wolfgang Otto, Robert Stoehr, Danijel Sikic, Bastian Keck, Sebastian Eidt, Maximilian Burger, Christian Bolenz, Katja Nitschke, Stefan Porubsky, Arndt Hartmann and Philipp Erben

Int. J. Mol. Sci. 2018, 19(11), 3396; https://doi.org/10.3390/ijms19113396 - 30 Oct 2018

Cited by 36 | Viewed by 3963

Abstract

Recently, muscle-invasive bladder cancer (MIBC) has been subclassified by gene expression profiling, with a substantial impact on therapy response and patient outcome. We tested whether these complex molecular subtypes of MIBC can be determined by mRNA detection of keratin 5 (KRT5) and keratin 20 (KRT20). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of KRT5 and KRT20 using TaqMan^®-based assays in 122 curatively treated MIBC patients (median age 68.0 years). Furthermore, in silico analysis of the MD Anderson Cancer Center (MDACC) cohort (GSE48277 + GSE47993) was performed. High expression of KRT5 and low expression of KRT20 were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS: 5-year DSS for KRT5 high: 58%; 5-year DSS for KRT20 high: 29%). KRT5 and KRT20 were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of KRT5 and KRT20 allowed identification of patients with a very poor prognosis (KRT20⁺/KRT5⁻, 5-year DSS 0%, p < 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for KRT20 low vs. high: 84% vs. 40%, p = 0.042). High KRT20-expressing tumors as well as KRT20⁺/KRT⁻ tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested). Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

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14 pages, 27266 KiB

Open AccessArticle

Diagnostic and Prognostic Implications of FGFR3^high/Ki67^high Papillary Bladder Cancers

by Mirja Geelvink, Armin Babmorad, Angela Maurer, Robert Stöhr, Tobias Grimm, Christian Bach, Ruth Knuechel, Michael Rose and Nadine T. Gaisa

Int. J. Mol. Sci. 2018, 19(9), 2548; https://doi.org/10.3390/ijms19092548 - 28 Aug 2018

Cited by 13 | Viewed by 4205

Abstract

Prognostic/therapeutic stratification of papillary urothelial cancers is solely based upon histology, despite activated FGFR3-signaling was found to be associated with low grade tumors and favorable outcome. However, there are FGFR3-overexpressing tumors showing high proliferation—a paradox of coexisting favorable and adverse features. Therefore, our study aimed to decipher the relevance of FGFR3-overexpression/proliferation for histopathological grading and risk stratification. N = 142 (n = 82 pTa, n = 42 pT1, n = 18 pT2-4) morphologically G1–G3 tumors were analyzed for immunohistochemical expression of FGFR3 and Ki67. Mutation analysis of FGFR3 and TP53 and FISH for FGFR3 amplification and rearrangement was performed. SPSS 23.0 was used for statistical analysis. Overall FGFR3^high/Ki67^high status (n = 58) resulted in a reduced ∆mean progression-free survival (PFS) (p < 0.01) of 63.92 months, and shorter progression-free survival (p < 0.01; mean PFS: 55.89 months) in pTa tumors (n = 50). FGFR3^mut/TP53^mut double mutations led to a reduced ∆mean PFS (p < 0.01) of 80.30 months in all tumors, and FGFR3^mut/TP53^mut pTa tumors presented a dramatically reduced PFS (p < 0.001; mean PFS: 5.00 months). Our results identified FGFR3^high/Ki67^high papillary pTa tumors as a subgroup with poor prognosis and encourage histological grading as high grade tumors. Tumor grading should possibly be augmented by immunohistochemical stainings and suitable clinical surveillance by endoscopy should be performed. Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

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12 pages, 1674 KiB

Open AccessArticle

Diagnostic and Prognostic Potential of MicroRNA Maturation Regulators Drosha, AGO1 and AGO2 in Urothelial Carcinomas of the Bladder

by Anja Rabien, Nadine Ratert, Anica Högner, Andreas Erbersdobler, Klaus Jung, Thorsten H. Ecke and Ergin Kilic

Int. J. Mol. Sci. 2018, 19(6), 1622; https://doi.org/10.3390/ijms19061622 - 31 May 2018

Cited by 7 | Viewed by 3381

Abstract

Bladder cancer still requires improvements in diagnosis and prognosis, because many of the cases will recur and/or metastasize with bad outcomes. Despite ongoing research on bladder biomarkers, the clinicopathological impact and diagnostic function of miRNA maturation regulators Drosha and Argonaute proteins AGO1 and AGO2 in urothelial bladder carcinoma remain unclear. Therefore, we conducted immunohistochemical investigations of a tissue microarray composed of 112 urothelial bladder carcinomas from therapy-naïve patients who underwent radical cystectomy or transurethral resection and compared the staining signal with adjacent normal bladder tissue. The correlations of protein expression of Drosha, AGO1 and AGO2 with sex, age, tumor stage, histological grading and overall survival were evaluated in order to identify their diagnostic and prognostic potential in urothelial cancer. Our results show an upregulation of AGO1, AGO2 and Drosha in non-muscle-invasive bladder carcinomas, while there was increased protein expression of only AGO2 in muscle-invasive bladder carcinomas. Moreover, we were able to differentiate between non-muscle-invasive and muscle-invasive bladder carcinoma according to AGO1 and Drosha expression. Finally, despite Drosha being a discriminating factor that can predict the probability of overall survival in the Kaplan–Meier analysis, AGO1 turned out to be independent of all clinicopathological parameters according to Cox regression. In conclusion, we assumed that the miRNA processing factors have clinical relevance as potential diagnostic and prognostic tools for bladder cancer. Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

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13 pages, 1156 KiB

Open AccessArticle

Evaluation of a New Survivin ELISA and UBC^® Rapid for the Detection of Bladder Cancer in Urine

by Jan Gleichenhagen, Christian Arndt, Swaantje Casjens, Carmen Meinig, Holger Gerullis, Irina Raiko, Thomas Brüning, Thorsten Ecke and Georg Johnen

Int. J. Mol. Sci. 2018, 19(1), 226; https://doi.org/10.3390/ijms19010226 - 11 Jan 2018

Cited by 25 | Viewed by 5130

Abstract

Urine-based biomarkers for non-invasive diagnosis of bladder cancer are urgently needed. No single marker with sufficient sensitivity and specificity has been described so far. Thus, a combination of markers appears to be a promising approach. The aim of this case-control study was to evaluate the performance of an in-house developed enzyme-linked immunosorbent assay (ELISA) for survivin, the UBC^® Rapid test, and the combination of both assays. A total of 290 patients were recruited. Due to prior bladder cancer, 46 patients were excluded. Urine samples were available from 111 patients with bladder cancer and 133 clinical controls without urologic diseases. Antibodies generated from recombinant survivin were utilized to develop a sandwich ELISA. The ELISA and the UBC^® Rapid test were applied to all urine samples. Receiver operating characteristic (ROC) analysis was used to evaluate marker performance. The survivin ELISA exhibited a sensitivity of 35% with a specificity of 98%. The UBC^® Rapid test showed a sensitivity of 56% and a specificity of 96%. Combination of both assays increased the sensitivity to 66% with a specificity of 95%. For high-grade tumors, the combination showed a sensitivity of 82% and a specificity of 95%. The new survivin ELISA and the UBC^® Rapid test are both able to detect bladder cancer, especially high-grade tumors. However, the performance of each individual marker is moderate and efforts to improve the survivin assay should be pursued. A combination of both assays confirmed the benefit of using marker panels. The results need further testing in a prospective study and with a high-risk population. Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

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Open AccessArticle

Aberrant N-Glycosylation Profile of Serum Immunoglobulins is a Diagnostic Biomarker of Urothelial Carcinomas

by Toshikazu Tanaka, Tohru Yoneyama, Daisuke Noro, Kengo Imanishi, Yuta Kojima, Shingo Hatakeyama, Yuki Tobisawa, Kazuyuki Mori, Hayato Yamamoto, Atsushi Imai, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Masakazu Tanaka, Shin-Ichiro Nishimura, Shizuka Kurauchi, Ippei Takahashi and Chikara Ohyama

Int. J. Mol. Sci. 2017, 18(12), 2632; https://doi.org/10.3390/ijms18122632 - 06 Dec 2017

Cited by 32 | Viewed by 4527

Abstract

The aim of this study to determine whether the aberrant N-glycosylated serum immunoglobulins (Igs) can be applied as a diagnostic marker of urothelial carcinoma (UC). Between 2009 and 2016, we randomly obtained serum available from 237 UC and also 96 prostate cancer as other cancer controls from our serum bank and also obtained—from 339 healthy volunteers (HV)—controls obtained from community-dwelling volunteers in Iwaki Health Promotion Project. A total of 32 types of N-glycan levels on Igs were determined by high-throughput N-glycomics and analyzed by multivariable discriminant analysis. We found five UC-associated aberrant N-glycans changes on Igs and also found that asialo-bisecting GlcNAc type N-glycan on Igs were significantly accumulated in UC patients. The diagnostic N-glycan Score (dNGScore) established by combination of five N-glycans on Igs discriminated UC patients from HV and prostate cancer (PC) patients with 92.8% sensitivity and 97.2% specificity. The area under the curve (AUC) for of the dNGScore was 0.969 for UC detection that was much superior to that of urine cytology (AUC, 0.707) and hematuria (AUC, 0.892). Furthermore, dNGScore can detect hematuria and urine cytology negative patients. The dNGscore based on aberrant N-glycosylation signatures of Igs were found to be promising diagnostic biomarkers of UCs. Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

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Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette-Guérin: A Long-Term Follow-Up Study of a Japanese Cohort

by Makito Miyake, Yoshihiro Tatsumi, Daisuke Gotoh, Sayuri Ohnishi, Takuya Owari, Kota Iida, Kenta Ohnishi, Shunta Hori, Yosuke Morizawa, Yoshitaka Itami, Yasushi Nakai, Takeshi Inoue, Satoshi Anai, Kazumasa Torimoto, Katsuya Aoki, Keiji Shimada, Noboru Konishi, Nobumichi Tanaka and Kiyohide Fujimoto

Int. J. Mol. Sci. 2017, 18(10), 2186; https://doi.org/10.3390/ijms18102186 - 19 Oct 2017

Cited by 64 | Viewed by 5739

Abstract

The clinical significance of regulatory T cells (Treg) and tumor-associated macrophages (TAM) in the tumor microenvironment of human bladder cancer remains unclear. The aim of this study is to explore their relevance to oncological features in non-muscle invasive bladder cancer (NMIBC). We carried out immunohistochemical analysis of forkhead box P3 (FOXP3, Treg maker), CD204 (TAM marker), and interleukin-6 (IL6) using surgical specimens obtained from 154 NMIBC patients. The Treg and TAM counts surrounding the cancer lesion and IL6-positive cancer cell counts were evaluated against clinicopathological variables. We focused on the ability of the Treg and TAM counts around the cancer lesion to predict outcomes after adjuvant intravesical Bacille Calmette–Guérin (BCG) treatment. High Treg counts were associated with female patients, older age, T1 category, and high tumor grade. TAM count was significantly correlated with Treg count and with IL6-positive cancer cell count. In our analysis of 71 patients treated with BCG, high counts of Treg and TAM were associated with shorter recurrence-free survival, and the former was an independent predictor of recurrence. Poor response to intravesical BCG was associated with Treg and TAM in the tumor microenvironment. Disrupting the immune network can be a supplementary therapeutic approach for NMIBC patients receiving intravesical BCG. Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

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Review

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Impact of Sarcopenia as a Prognostic Biomarker of Bladder Cancer

by Hiroshi Fukushima, Kosuke Takemura, Hiroaki Suzuki and Fumitaka Koga

Int. J. Mol. Sci. 2018, 19(10), 2999; https://doi.org/10.3390/ijms19102999 - 01 Oct 2018

Cited by 45 | Viewed by 7484

Abstract

Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates patient frailty and impaired physical function. Sarcopenia can be caused by multiple factors, including advanced age, lack of exercise, poor nutritional status, inflammatory diseases, endocrine diseases, and malignancies. In patients with cancer cachexia, anorexia, poor nutrition and systemic inflammation make the metabolic state more catabolic, resulting in sarcopenia. Thus, sarcopenia is considered as one of manifestations of cancer cachexia. Recently, growing evidence has indicated the importance of sarcopenia in the management of patients with various cancers. Sarcopenia is associated with not only higher rates of treatment-related complications but also worse prognosis in cancer-bearing patients. In this article, we summarized metabolic backgrounds of cancer cachexia and sarcopenia and definitions of sarcopenia based on computed tomography (CT) images. We conducted a systematic literature review regarding the significance of sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent studies focusing on the prognostic role of changes in skeletal muscle mass during the course of treatment in bladder cancer patients. Lastly, we discussed the impact of nutritional support, medication, and exercise on sarcopenia in cancer-bearing patients. Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

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18 pages, 1490 KiB

Open AccessReview

Extracellular Vesicles in Bladder Cancer: Biomarkers and Beyond

by Yu-Ru Liu, Carlos J. Ortiz-Bonilla and Yi-Fen Lee

Int. J. Mol. Sci. 2018, 19(9), 2822; https://doi.org/10.3390/ijms19092822 - 18 Sep 2018

Cited by 33 | Viewed by 6781

Abstract

Tumor-derived extracellular vesicles (TEVs) are membrane-bound, nanosized vesicles released by cancer cells and taken up by cells in the tumor microenvironment to modulate the molecular makeup and behavior of recipient cells. In this report, we summarize the pivotal roles of TEVs involved in bladder cancer (BC) development, progression and treatment resistance through transferring their bioactive cargos, including proteins and nucleic acids. We also report on the molecular profiling of TEV cargos derived from urine and blood of BC patients as non-invasive disease biomarkers. The current hurdles in EV research and plausible solutions are discussed. Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

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13 pages, 1254 KiB

Open AccessReview

Biomarkers for Predicting Clinical Outcomes of Chemoradiation-Based Bladder Preservation Therapy for Muscle-Invasive Bladder Cancer

by Fumitaka Koga, Kosuke Takemura and Hiroshi Fukushima

Int. J. Mol. Sci. 2018, 19(9), 2777; https://doi.org/10.3390/ijms19092777 - 15 Sep 2018

Cited by 13 | Viewed by 3985

Abstract

Chemoradiation-based bladder preservation therapy (BPT) is currently a curative option for non-metastatic muscle-invasive bladder cancer (MIBC) patients at favorable risk or an alternative to radical cystectomy (RC) for those who are unfit for RC. In BPT, only patients who achieve complete response (CR) after chemoradiation have a favorable prognosis and quality of life with a preserved functional bladder. Thus, predicting CR and favorable prognosis is important for optimal patient selection for BPT. We reviewed biomarkers for predicting the clinical outcomes of chemoradiation-based BPT. The biomarkers studied were categorized into those related to apoptosis, cell proliferation, receptor tyrosine kinases, DNA damage response genes, hypoxia, molecular subtype, and others. Among these biomarkers, the Ki-67 labeling index (Ki-67 LI) and meiotic recombination 11 may be used for selecting BPT or RC. Ki-67 LI and erythroblastic leukemia viral oncogene homolog 2 (erbB2) may be used for predicting both the chemoradiation response and the prognosis of patients on BPT. Concurrent use of trastuzumab and a combination of carbogen and nicotinamide can overcome chemoradiation resistance conferred by erbB2 overexpression and tumor hypoxia. Further studies are needed to confirm the practical utility of these biomarkers for progress on biomarker-directed personalized management of MIBC patients. Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

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14 pages, 220 KiB

Open AccessReview

Circulating Tumour DNA in Muscle-Invasive Bladder Cancer

by Melissa P. Tan, Gerhardt Attard and Robert A. Huddart

Int. J. Mol. Sci. 2018, 19(9), 2568; https://doi.org/10.3390/ijms19092568 - 29 Aug 2018

Cited by 15 | Viewed by 3294

Abstract

Circulating tumour DNA (ctDNA) is an attractive tool in cancer research, offering many advantages over tissue samples obtained using traditional biopsy methods. There has been increasing interest in its application to muscle-invasive bladder cancer (MIBC), which is recognised to be a heterogeneous disease with overall poor prognosis. Using a range of platforms, studies have shown that ctDNA is detectable in MIBC and may be a useful biomarker in monitoring disease status and guiding treatment decisions in MIBC patients. Currently, with no such predictive or prognostic biomarkers in clinical practice to guide treatment strategy, there is a real unmet need for a personalised medicine approach in MIBC, and ctDNA offers an exciting avenue through which to pursue this goal. In this article, we present an overview of work to date on ctDNA in MIBC, and discuss the inherent challenges present as well as the potential future clinical applications. Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

34 pages, 1860 KiB

Open AccessReview

Liquid Biopsy Biomarkers in Bladder Cancer: A Current Need for Patient Diagnosis and Monitoring

by Iris Lodewijk, Marta Dueñas, Carolina Rubio, Ester Munera-Maravilla, Cristina Segovia, Alejandra Bernardini, Alicia Teijeira, Jesús M. Paramio and Cristian Suárez-Cabrera

Int. J. Mol. Sci. 2018, 19(9), 2514; https://doi.org/10.3390/ijms19092514 - 24 Aug 2018

Cited by 69 | Viewed by 7553

Abstract

Bladder Cancer (BC) represents a clinical and social challenge due to its high incidence and recurrence rates, as well as the limited advances in effective disease management. Currently, a combination of cytology and cystoscopy is the routinely used methodology for diagnosis, prognosis and disease surveillance. However, both the poor sensitivity of cytology tests as well as the high invasiveness and big variation in tumour stage and grade interpretation using cystoscopy, emphasizes the urgent need for improvements in BC clinical guidance. Liquid biopsy represents a new non-invasive approach that has been extensively studied over the last decade and holds great promise. Even though its clinical use is still compromised, multiple studies have recently focused on the potential application of biomarkers in liquid biopsies for BC, including circulating tumour cells and DNA, RNAs, proteins and peptides, metabolites and extracellular vesicles. In this review, we summarize the present knowledge on the different types of biomarkers, their potential use in liquid biopsy and clinical applications in BC. Full article

(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision)

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