A5048804324- Bladder and Urothelial Cancer Treatments
- Cancer Genomics and Diagnostics
- Urinary and Genital Oncology Studies
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Renal cell carcinoma treatment
- Esophageal Cancer Research and Treatment
- Ferroptosis and cancer prognosis
- Cancer Research and Treatments
- Single-cell and spatial transcriptomics
- Molecular Biology Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Immune Cell Function and Interaction
- Immune cells in cancer
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Fibroblast Growth Factor Research
- Gene expression and cancer classification
- Cancer, Lipids, and Metabolism
- Colorectal Cancer Treatments and Studies
- Cancer Cells and Metastasis
- Urological Disorders and Treatments
- Computational Drug Discovery Methods
Aarhus University Hospital
2019-2025
Aarhus University
2020-2025
PURPOSE Novel sensitive methods for early detection of relapse and monitoring therapeutic efficacy may have a huge impact on risk stratification, treatment, ultimately outcome patients with bladder cancer. We addressed the prognostic predictive ultra-deep sequencing cell-free DNA in before after cystectomy during chemotherapy. PATIENTS AND METHODS included 68 localized advanced Patient-specific somatic mutations, identified by whole-exome sequencing, were used to assess circulating tumor...
Abstract The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed NMIBC ( n = 834). Transcriptomic identifies four classes (1, 2a, 2b and 3) reflecting tumor biology disease aggressiveness. Both transcriptome-based subtyping the level chromosomal instability provide independent prognostic value beyond established...
Overtreatment with cisplatin-based chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC), and currently none reported biomarkers for predicting response have been implemented clinic. Here we perform comprehensive multi-omics analysis (genomics, transcriptomics, epigenomics proteomics) 300 MIBC patients treated (neoadjuvant or first-line) to identify molecular changes associated treatment response. DNA-based associations converge on genomic instability...
Circulating tumor DNA (ctDNA) can be used for sensitive detection of minimal residual disease (MRD). However, the probability detecting ctDNA in settings low burden is limited by number mutations analyzed and plasma volume available. We a whole-genome sequencing (WGS) approach patients with urothelial carcinoma.
The functional status of immune cells in the tumor microenvironment and characteristics may explain bacillus Calmette-Guérin (BCG) failure high-risk non-muscle-invasive bladder cancer (NMIBC).To characterize molecular correlates post-BCG high-grade (HG) recurrence using multiomics analysis.Patients with BCG-treated NMIBC (n = 156) were included study. Metachronous tumors analyzed RNA sequencing 170) whole-exome 195). Urine samples for immuno-oncology-related proteins 190) tumor-derived DNA...
Abstract Purpose: To investigate the use of plasma and urine DNA mutation analysis for predicting neoadjuvant chemotherapy (NAC) response oncological outcome in patients with muscle-invasive bladder cancer. Experimental Design: Whole-exome sequencing tumor germline was performed 92 treated NAC followed by radical cystectomy (RC). A custom NGS-panel capturing approximately 50 mutations per patient designed used to track mutated urine. total 447 samples, 281 supernatants, 123 pellets collected...
Abstract Purpose: To investigate whether circulating tumor DNA (ctDNA) assessment in patients with muscle-invasive bladder cancer predicts treatment response and provides early detection of metastatic disease. Experimental Design: We present full follow-up results (median follow-up: 68 months) from a previously described cohort neoadjuvant chemotherapy (NAC)-treated who underwent longitudinal ctDNA testing (712 plasma samples). In addition, we performed evaluation 153 samples collected...
Field cancerization is characterized by areas of normal tissue affected mutated clones. Bladder field may explain the development and recurrence bladder cancer be associated with treatment outcomes.
Understanding the molecular determinants that underpin clinical heterogeneity of non-muscle-invasive bladder cancer (NMIBC) is essential for prognostication and therapy development. Stage T1 disease in particular presents a high risk progression requires improved understanding. We present detailed multi-omics study containing gene expression, copy number, mutational profiles show relationships to immune infiltration, recurrence, muscle invasion. compare expression genomic subtypes derived...
Current bulk transcriptomic classification systems for bladder cancer do not consider the level of intratumor subtype heterogeneity.To investigate extent and possible clinical impact heterogeneity across early more advanced stages cancer.We performed single-nucleus RNA sequencing (RNA-seq) 48 tumors additional spatial transcriptomics four these tumors. Total RNA-seq proteomics data were available from same comparison, along with detailed follow-up patients.The primary outcome was...
Abstract Introduction: Circulating tumor DNA (ctDNA) has demonstrated significant potential for early relapse detection and therapeutic monitoring in patients with muscle-invasive bladder cancer (MIBC). Advancing its clinical utility requires examining factors that may affect plasma ctDNA levels, including those influencing clearance. Here, we evaluated the association between kidney liver function markers MIBC patients. Secondly, explored immune markers, as well prognostic of biochemical...
Abstract Introduction: There is a critical need for biomarkers to assess treatment efficacy and detect minimal residual disease (MRD), enabling timely initiation response monitoring. Tumor-informed detection of mutations in cell-free DNA (cfDNA) has shown promise monitoring MRD. In the TOMBOLA trial (NCT04138628), circulating tumor (ctDNA) detected using patient-specific droplet digital PCR (ddPCR) guide immunotherapy. However, due design process personalized ddPCR assays, standardization...
Abstract Introduction& objectives: The gold standard treatment for non-metastatic muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Despite this aggressive treatment, approximately 50% of patients develop metastases within the first 2 years follow-up. Adjuvant immunotherapy recommended at high risk recurrence after cystectomy, while remaining typically receive only visible detected. In study, we investigated use circulating tumor...
563 Background: Muscle-invasive bladder cancer (MIBC) accounts for ~25–30% of all diagnoses. With neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) as standard-of-care, the 5-year survival rate ranges from 40%–60%. Bladder-sparing protocols (BSP) have emerged a feasible alternative to RC MIBC treatment, however better tools are needed. In this study, we evaluated prognostic value circulating tumor DNA (ctDNA) in predicting recurrence patients who achieved pathological...
Bladder cancer (BCa) is more common in men and presents differences molecular subtypes based on sex. Fibroblast growth factor receptor 3 (FGFR3) mutations are enriched the luminal papillary muscle-invasive BCa (MIBC) non-MIBC subtypes.To determine whether FGFR3 initiate impact male sex bias.We developed a transgenic mouse model expressing most frequent mutation, FGFR3-S249C, urothelial cells. tumorigenesis was monitored mice, with without carcinogen exposure. Mouse human transcriptomic data...
This paper provides a laboratory workflow for single-nucleus RNA-sequencing (snRNA-seq) including protocol gentle nuclei isolation from fresh frozen tumor biopsies, making it possible to analyze biobanked material. To develop this protocol, we used non-frozen and human bladder tumors cell lines. We tested different lysis buffers (IgePal Nuclei EZ) incubation times in combination with approaches tissue dissection: sectioning, semi-automated dissociation, manual dissociation pestles, combined...
Abstract The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we performed a integrative multi-omics analysis of patients diagnosed NMIBC (n=834). Transcriptomic identified four classes (1, 2a, 2b and 3) reflecting tumor biology disease aggressiveness. Both transcriptome-based subtyping the level chromosomal instability provided independent prognostic value beyond established...
Abstract Background Circulating tumor DNA (ctDNA) analysis is an emerging field for diagnosis, monitoring of treatment efficacy and detection disease recurrence in various cancers. In bladder cancer, previous work has demonstrated prognostic value ctDNA early stage cancers following radical cystectomy (CX), however more extensive investigation the potential impact on clinical decision making remains to be carried out. Methods A total 68 patients with localized advanced cancer treated...
Abstract Circulating tumor DNA (ctDNA) can be used for sensitive detection of minimal residual disease (MRD). However, the probability detecting ctDNA at low burden is limited by number mutations analyzed and available plasma volume. Here we applied a tumor-informed whole genome sequencing (WGS) approach ctDNA-based MRD (91% sensitivity, 92% specificity) treatment response evaluation in 916 longitudinally collected samples from 112 patients with localized muscle-invasive bladder cancer. We...