ijms-logo

Journal Browser

Journal Browser

Molecular Diagnostics and Therapeutic Target in Bladder Cancer

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 May 2024) | Viewed by 12704

Special Issue Editor


E-Mail Website
Guest Editor
1. Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
2. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Interests: urinary biomarkers for early detection, prognostics, and prediction of the response to treatment of bladder cancer; the role of sphingolipid signaling cascade in cancers, such as colon, breast, and bladder
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bladder cancer is the 6th and 10th most common cancer type in the US and worldwide, respectively. Bladder cancer represents one of the most challenging and expensive cancers to diagnose and treat because of its high recurrence rate. Most bladder cancers are diagnosed at an early stage, when they are highly treatable. However, about 25% of bladder cancers are diagnosed at later stages. When detected early (i.e., non-muscle invasive bladder cancer, NMIBC or stage 1), the 5-year survival rate is approximately 94%, compared to at best a 50% 5-year survival rate when the disease is noted to be muscle-invasive bladder cancer (MIBC, stage 2) and a less than 20% 5-year survival rate when the disease is metastatic (stages 3 and 4). Therefore, it is very important to detect bladder cancer at an early stage and to carefully monitor patients. However, currently bladder cancer diagnosis relies mainly on cystoscopy, an invasive and expensive procedure. Thus, there is an unmet need for non-invasive and accurate bladder cancer diagnosis techniques. In addition, many new drugs for bladder cancer have been introduced to clinical practice past several years, but they are mainly for the treatment of MIBC. The treatment for NMIBC still relies on transurethral resection followed by intravesical bacillus Calmette-Guerin (BCG). Thus, new therapeutics for NMIBC must be developed. Taken all together, this Special Issue is inviting research papers on molecular diagnostics and therapeutic target in bladder cancer, including but not limited to the biomarkers for early detection and progression, new therapeutic targets as well as first-in-class medications.

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

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • non-muscle invasive bladder cancer
  • muscle invasive bladder cancer
  • metastatic bladder cancer
  • diagnostic biomarkers
  • therapeutic targets

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (8 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

19 pages, 2670 KiB  
Article
Prognostic and Predictive Potential of CCL5 Expression in Muscle-Invasive Bladder Cancer Patients
by Cedric Smolka, Markus Eckstein, Rudolf Jung, Verena Lieb, Danijel Sikic, Robert Stöhr, Veronika Bahlinger, Simone Bertz, Astrid Kehlen, Arndt Hartmann, Bernd Wullich, Helge Taubert and Sven Wach
Int. J. Mol. Sci. 2024, 25(12), 6325; https://doi.org/10.3390/ijms25126325 - 7 Jun 2024
Cited by 1 | Viewed by 1133
Abstract
Bladder cancer (BC) is the 12th most commonly diagnosed cancer worldwide. Although there are several well-established molecular and immunological classifications, prognostic and predictive markers for tumor cells and immune cells are still needed. Using a tissue microarray, we analyzed the expression of the [...] Read more.
Bladder cancer (BC) is the 12th most commonly diagnosed cancer worldwide. Although there are several well-established molecular and immunological classifications, prognostic and predictive markers for tumor cells and immune cells are still needed. Using a tissue microarray, we analyzed the expression of the chemokine CC motif ligand 5 (CCL5) by immunohistochemistry (IHC) in 175 muscle-invasive BC samples. The application of a single cutoff for the staining status of tumor cells (TCs; positive vs. negative) and immune cells (ICs; positive vs. negative) revealed 75 patients (42.9%) and 123 patients (70.3%) with CCL5-positive TCs or ICs, respectively. IHC results were associated with prognostic and predictive data. Multivariate Cox regression analysis revealed that positive CCL5 staining in TCs was associated with significantly shorter disease-specific survival (DSS; RR = 1.51; p = 0.047), but CCL5-negative ICs were associated with significantly shorter overall survival (OS; RR = 1.66; p = 0.005), DSS (RR = 2.02; p = 0.001) and recurrence-free survival (RFS; RR = 1.94; p = 0.002). Adjuvant chemotherapy was favorable for patients with CCL5-negative ICs for OS (RR = 0.30; p = 0.006), DSS (RR = 0.36; p = 0.022) and RFS (RR = 0.41; p = 0.046) but not for patients with CCL5-positive ICs, except in the subgroup of N1 + N2 patients, where it was associated with better OS. We suggest that CCL5 expression can be a prognostic and predictive marker for muscle-invasive bladder cancer patients. Full article
(This article belongs to the Special Issue Molecular Diagnostics and Therapeutic Target in Bladder Cancer)
Show Figures

Figure 1

13 pages, 1781 KiB  
Communication
Enhancing Therapeutic Efficacy and Safety of Immune Checkpoint Inhibition for Bladder Cancer: A Comparative Analysis of Injectable vs. Intravesical Administration
by Pradeep Tyagi, Jason Hafron, Jonathan Kaufman and Michael Chancellor
Int. J. Mol. Sci. 2024, 25(9), 4945; https://doi.org/10.3390/ijms25094945 - 1 May 2024
Viewed by 1588
Abstract
Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. While Bacillus Calmette–Guérin (BCG) remains a cornerstone of BC therapy, resistance [...] Read more.
Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. While Bacillus Calmette–Guérin (BCG) remains a cornerstone of BC therapy, resistance poses a challenge, necessitating alternative strategies. Immune checkpoint inhibitors (ICIs) have shown promise, yet systemic toxicity raises concern. Intravesical administration of ICIs offers a potential solution, with recent studies demonstrating the feasibility and efficacy of intravesical pembrolizumab. Although systemic toxicity remains a concern, its localized administration may mitigate adverse events. Additionally, liposomal delivery of ICIs exhibits promises in enhancing drug penetration and reducing toxicity. Novel imaging modalities compatible with Vesical Imaging-Reporting and Data System (VI-RADS) and capable of predicting high-grade bladder cancer can aid the pre-operative shared decision making of patient and surgeon. Future research should focus on refining treatment approaches, optimizing dosing regimens, and leveraging advanced imaging techniques to improve patient outcomes. In conclusion, intravesical immunotherapy presents a promising avenue for BC treatment, offering enhanced therapeutic effectiveness while minimizing systemic toxicity. Continued research efforts are essential to validate these findings and optimize intravesical immunotherapy’s role in BC management, ultimately improving patient outcomes. Full article
(This article belongs to the Special Issue Molecular Diagnostics and Therapeutic Target in Bladder Cancer)
Show Figures

Figure 1

16 pages, 6383 KiB  
Article
Change in Tissue Microbiome and Related Human Beta Defensin Levels Induced by Antibiotic Use in Bladder Carcinoma
by Ádám Monyók, Bassel Mansour, István Vadnay, Nóra Makra, Zsuzsanna A. Dunai, Éva Nemes-Nikodém, Balázs Stercz, Dóra Szabó and Eszter Ostorházi
Int. J. Mol. Sci. 2024, 25(8), 4562; https://doi.org/10.3390/ijms25084562 - 22 Apr 2024
Viewed by 1066
Abstract
It is now generally accepted that the success of antitumor therapy can be impaired by concurrent antibiotic therapy, the presence of certain bacteria, and elevated defensin levels around the tumor tissue. The aim of our current investigation was to identify the underlying changes [...] Read more.
It is now generally accepted that the success of antitumor therapy can be impaired by concurrent antibiotic therapy, the presence of certain bacteria, and elevated defensin levels around the tumor tissue. The aim of our current investigation was to identify the underlying changes in microbiome and defensin levels in the tumor tissue induced by different antibiotics, as well as the duration of this modification. The microbiome of the tumor tissues was significantly different from that of healthy volunteers. Comparing only the tumor samples, no significant difference was confirmed between the untreated group and the group treated with antibiotics more than 3 months earlier. However, antibiotic treatment within 3 months of analysis resulted in a significantly modified microbiome composition. Irrespective of whether Fosfomycin, Fluoroquinolone or Beta-lactam treatment was used, the abundance of Bacteroides decreased, and Staphylococcus abundance increased. Large amounts of the genus Acinetobacter were observed in the Fluoroquinolone-treated group. Regardless of the antibiotic treatment, hBD1 expression of the tumor cells consistently doubled. The increase in hBD2 and hBD3 expression was the highest in the Beta-lactam treated group. Apparently, antibiotic treatment within 3 months of sample analysis induced microbiome changes and defensin expression levels, depending on the identity of the applied antibiotic. Full article
(This article belongs to the Special Issue Molecular Diagnostics and Therapeutic Target in Bladder Cancer)
Show Figures

Figure 1

17 pages, 1919 KiB  
Article
Differential Expression of CKLF-like MARVEL Transmembrane Domain-Containing Protein 6 and Programmed Cell Death Ligand 1 as Prognostic Biomarkers in Upper Tract Urothelial Carcinoma
by Said Kdimati, Clemens Christoph, Änne Glass, Nadja Engel, Desiree-Louise Dräger, Claudia Maletzki, Anne-Sophie Becker and Annette Zimpfer
Int. J. Mol. Sci. 2024, 25(6), 3492; https://doi.org/10.3390/ijms25063492 - 20 Mar 2024
Cited by 1 | Viewed by 1118
Abstract
Upper tract urothelial carcinoma (UTUC) accounts for 5–10% of all UCs. Immune checkpoint inhibitors (ICIs) have been established for UCs. The prognostic and predictive potential of programmed cell death ligand 1 (PD-L1) expression to stratify patients benefiting from ICIs is not fully understood, [...] Read more.
Upper tract urothelial carcinoma (UTUC) accounts for 5–10% of all UCs. Immune checkpoint inhibitors (ICIs) have been established for UCs. The prognostic and predictive potential of programmed cell death ligand 1 (PD-L1) expression to stratify patients benefiting from ICIs is not fully understood, and additional markers influencing the impact of PD-L1-mediated ICI response are needed. Previously, the chemokine-like MARVEL transmembrane domain-containing protein 6 (CMTM6) was identified as a positive regulator of PD-L1. Our aim was to investigate the expression profiles and impact of PD-L1 and CMTM6 protein status on the prognostic parameters and survival of UTUC patients. In this retrospective study, the combined positive score (CPS), tumor proportion score (TPS), and immune cell score (ICS) for PD-L1 and CMTM6 were determined. High PD-L1 CPS, ICS, and TPS were found in 77.4%, 58.3%, and 45.2% of cases, and high CMTM6 CPS, ICS, and TPS were seen in 52.5%, 51.5%, and 55.5% of cases, respectively. The scores of both markers had a significant positive correlation. High PD-L1 and CMTM6 expression was coupled with higher pT status, WHO grade, necrosis, and metastasis (p < 0.05, respectively). In the univariate survival analysis, patients with a PD-L1 ICS high and higher degree of intratumoral inflammation showed significantly longer overall survival. Compared to other studies on UC, our study shows a substantially higher rate of PD-L1-positive tumors. CMTM6 was associated with more aggressive tumors. Full article
(This article belongs to the Special Issue Molecular Diagnostics and Therapeutic Target in Bladder Cancer)
Show Figures

Figure 1

15 pages, 4721 KiB  
Article
MRI/RNA-Seq-Based Radiogenomics and Artificial Intelligence for More Accurate Staging of Muscle-Invasive Bladder Cancer
by Touseef Ahmad Qureshi, Xingyu Chen, Yibin Xie, Kaoru Murakami, Toru Sakatani, Yuki Kita, Takashi Kobayashi, Makito Miyake, Simon R. V. Knott, Debiao Li, Charles J. Rosser and Hideki Furuya
Int. J. Mol. Sci. 2024, 25(1), 88; https://doi.org/10.3390/ijms25010088 - 20 Dec 2023
Viewed by 1710
Abstract
Accurate staging of bladder cancer assists in identifying optimal treatment (e.g., transurethral resection vs. radical cystectomy vs. bladder preservation). However, currently, about one-third of patients are over-staged and one-third are under-staged. There is a pressing need for a more accurate staging modality to [...] Read more.
Accurate staging of bladder cancer assists in identifying optimal treatment (e.g., transurethral resection vs. radical cystectomy vs. bladder preservation). However, currently, about one-third of patients are over-staged and one-third are under-staged. There is a pressing need for a more accurate staging modality to evaluate patients with bladder cancer to assist clinical decision-making. We hypothesize that MRI/RNA-seq-based radiogenomics and artificial intelligence can more accurately stage bladder cancer. A total of 40 magnetic resonance imaging (MRI) and matched formalin-fixed paraffin-embedded (FFPE) tissues were available for analysis. Twenty-eight (28) MRI and their matched FFPE tissues were available for training analysis, and 12 matched MRI and FFPE tissues were used for validation. FFPE samples were subjected to bulk RNA-seq, followed by bioinformatics analysis. In the radiomics, several hundred image-based features from bladder tumors in MRI were extracted and analyzed. Overall, the model obtained mean sensitivity, specificity, and accuracy of 94%, 88%, and 92%, respectively, in differentiating intra- vs. extra-bladder cancer. The proposed model demonstrated improvement in the three matrices by 17%, 33%, and 25% and 17%, 16%, and 17% as compared to the genetic- and radiomic-based models alone, respectively. The radiogenomics of bladder cancer provides insight into discriminative features capable of more accurately staging bladder cancer. Additional studies are underway. Full article
(This article belongs to the Special Issue Molecular Diagnostics and Therapeutic Target in Bladder Cancer)
Show Figures

Figure 1

32 pages, 7822 KiB  
Article
OncoTherad® (MRB-CFI-1) Nanoimmunotherapy: A Promising Strategy to Treat Bacillus Calmette–Guérin-Unresponsive Non-Muscle-Invasive Bladder Cancer: Crosstalk among T-Cell CX3CR1, Immune Checkpoints, and the Toll-Like Receptor 4 Signaling Pathway
by João Carlos Cardoso Alonso, Bianca Ribeiro de Souza, Ianny Brum Reis, Gabriela Cardoso de Arruda Camargo, Gabriela de Oliveira, Maria Izabel de Barros Frazão Salmazo, Juliana Mattoso Gonçalves, José Ronaldo de Castro Roston, Paulo Henrique Ferreira Caria, André da Silva Santos, Leandro Luiz Lopes de Freitas, Athanase Billis, Nelson Durán and Wagner José Fávaro
Int. J. Mol. Sci. 2023, 24(24), 17535; https://doi.org/10.3390/ijms242417535 - 15 Dec 2023
Cited by 3 | Viewed by 2871
Abstract
This study assessed the safety and efficacy of OncoTherad® (MRB-CFI-1) nanoimmunotherapy for non-muscle invasive bladder cancer (NMIBC) patients unresponsive to Bacillus Calmette-Guérin (BCG) and explored its mechanisms of action in a bladder cancer microenvironment. A single-arm phase I/II study was conducted with [...] Read more.
This study assessed the safety and efficacy of OncoTherad® (MRB-CFI-1) nanoimmunotherapy for non-muscle invasive bladder cancer (NMIBC) patients unresponsive to Bacillus Calmette-Guérin (BCG) and explored its mechanisms of action in a bladder cancer microenvironment. A single-arm phase I/II study was conducted with 44 patients with NMIBC who were unresponsive to BCG treatment. Primary outcomes were pathological complete response (pCR) and relapse-free survival (RFS). Secondary outcomes comprised response duration and therapy safety. Patients’ mean age was 65 years; 59.1% of them were refractory, 31.8% relapsed, and 9.1% were intolerant to BCG. Moreover, the pCR rate after 24 months reached 72.7% (95% CI), whereas the mean RFS reached 21.4 months. Mean response duration in the pCR group was 14.3 months. No patient developed muscle-invasive or metastatic disease during treatment. Treatment-related adverse events occurred in 77.3% of patients, mostly grade 1–2 events. OncoTherad® activated the innate immune system through toll-like receptor 4, leading to increased interferon signaling. This activation played a crucial role in activating CX3CR1+ CD8 T cells, decreasing immune checkpoint molecules, and reversing immunosuppression in the bladder microenvironment. OncoTherad® has proved to be a safe and effective therapeutic option for patients with BCG-unresponsive NMIBC, besides showing likely advantages in tumor relapse prevention processes. Full article
(This article belongs to the Special Issue Molecular Diagnostics and Therapeutic Target in Bladder Cancer)
Show Figures

Figure 1

18 pages, 7241 KiB  
Article
Elucidating the Associated Biological Function and Clinical Significance of RHOJ Expression in Urothelial Carcinoma
by Xin-Jie Lu, Hsing-Fan Lai, Sheng-Cheng Wu, Chin-Li Chen and Yi-Lin Chiu
Int. J. Mol. Sci. 2023, 24(18), 14081; https://doi.org/10.3390/ijms241814081 - 14 Sep 2023
Cited by 1 | Viewed by 1395
Abstract
Urothelial cancer, a common urinary system malignancy, often presents treatment challenges due to metastasis and chemotherapy side effects. Angiogenesis, crucial for tumor growth, has become a target for drug development. This study explores the expression, prognostic value, and clinical correlation of RHOJ in [...] Read more.
Urothelial cancer, a common urinary system malignancy, often presents treatment challenges due to metastasis and chemotherapy side effects. Angiogenesis, crucial for tumor growth, has become a target for drug development. This study explores the expression, prognostic value, and clinical correlation of RHOJ in the TCGA BLCA, GSE31684, and GSE32894 datasets. We identify common differentially expressed genes across these databases and utilize g:Profiler and Cytoscape ClueGO for functional assessment. Further, we perform a gene set enrichment analysis (GSEA) using Hallmark gene sets and use the imsig package for immune cell infiltration analysis. Our analysis indicates that RHOJ expression levels significantly impact survival rates, tumor progression, and immune response in urothelial tumors. High RHOJ expression correlated with poor prognosis, advanced disease stages, and an increase in monocyte population within the tumor microenvironment. This aligns with current literature indicating a key role of immune infiltration in bladder cancer progression and treatment response. Moreover, the GSEA and imsig results further suggest a potential mechanistic link between RHOJ expression and immune-related pathways. Considering the increasing emphasis on immunotherapeutic strategies in bladder cancer management, our findings on RHOJ’s potential as a diagnostic biomarker and its association with immune response open new avenues for therapeutic interventions. Full article
(This article belongs to the Special Issue Molecular Diagnostics and Therapeutic Target in Bladder Cancer)
Show Figures

Figure 1

Review

Jump to: Research

18 pages, 558 KiB  
Review
Protein-Based Predictive Biomarkers to Personalize Neoadjuvant Therapy for Bladder Cancer—A Systematic Review of the Current Status
by Stacy Bedore, Joshua van der Eerden, Faizan Boghani, Saloni J. Patel, Samer Yassin, Karina Aguilar and Vinata B. Lokeshwar
Int. J. Mol. Sci. 2024, 25(18), 9899; https://doi.org/10.3390/ijms25189899 - 13 Sep 2024
Viewed by 930
Abstract
The clinical outcome of patients with muscle-invasive bladder cancer (MIBC) is poor despite the approval of neoadjuvant chemotherapy or immunotherapy to improve overall survival after cystectomy. MIBC subtypes, immune, transcriptome, metabolomic signatures, and mutation burden have the potential to predict treatment response but [...] Read more.
The clinical outcome of patients with muscle-invasive bladder cancer (MIBC) is poor despite the approval of neoadjuvant chemotherapy or immunotherapy to improve overall survival after cystectomy. MIBC subtypes, immune, transcriptome, metabolomic signatures, and mutation burden have the potential to predict treatment response but none have been incorporated into clinical practice, as tumor heterogeneity and lineage plasticity influence their efficacy. Using the PRISMA statement, we conducted a systematic review of the literature, involving 135 studies published within the last five years, to identify studies reporting on the prognostic value of protein-based biomarkers for response to neoadjuvant therapy in patients with MIBC. The studies were grouped based on biomarkers related to molecular subtypes, cancer stem cell, actin-cytoskeleton, epithelial–mesenchymal transition, apoptosis, and tumor-infiltrating immune cells. These studies show the potential of protein-based biomarkers, especially in the spatial context, to reduce the influence of tumor heterogeneity on a biomarker’s prognostic capability. Nevertheless, currently, there is little consensus on the methodology, reagents, and the scoring systems to allow reliable assessment of the biomarkers of interest. Furthermore, the small sample size of several studies necessitates the validation of potential prognostic biomarkers in larger multicenter cohorts before their use for individualizing neoadjuvant therapy regimens for patients with MIBC. Full article
(This article belongs to the Special Issue Molecular Diagnostics and Therapeutic Target in Bladder Cancer)
Show Figures

Figure 1

Back to TopTop