A5043316962- Bladder and Urothelial Cancer Treatments
- Cancer Immunotherapy and Biomarkers
- Urinary and Genital Oncology Studies
- Epigenetics and DNA Methylation
- Esophageal Cancer Research and Treatment
- Cancer Genomics and Diagnostics
- Renal cell carcinoma treatment
- Immune Cell Function and Interaction
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- Prenatal Screening and Diagnostics
- Prostate Cancer Treatment and Research
- Immune responses and vaccinations
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Cancer Research and Treatments
- Cancer-related molecular mechanisms research
- Cytomegalovirus and herpesvirus research
- Colorectal Cancer Screening and Detection
- Folate and B Vitamins Research
- Adipose Tissue and Metabolism
- Cancer Cells and Metastasis
- Kruppel-like factors research
Aarhus University
2017-2025
Aarhus University Hospital
2019-2025
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...
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...
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.
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...
Urothelial carcinoma in situ (CIS) is an aggressive phenotype of non-muscle-invasive bladder cancer. Molecular features unique to CIS compared high-grade papillary tumors are underexplored. RNA sequencing CIS, tumors, and normal urothelium showed lower immune marker expression tumors. We identified a 46-gene signature samples including selectively upregulated known druggable targets MTOR, TYK2, AXIN1, CPT1B, GAK, PIEZO1 downregulated BRD2 NDUFB2. High selected genes was significantly...
Abstract Introduction: The recommended treatment for high-risk non-muscle invasive bladder cancer (NMIBC) includes intravesical instillations of Bacillus Calmette-Guérin (BCG). Despite completing BCG therapy, up to 40 % patients experience disease recurrence within five years. T cell exhaustion has been associated with poor outcome following BCG. In this study, we investigated whether exhaustion, characterized by protein expression PD-1 and PD-L1 in paired samples obtained before after could...
Abstract T cells are central to the endogenous antitumor response and can recognize cancer neoantigens through their receptors (TCRs). Studies in multiple types have shown an association between TCR repertoire disease outcome, but remains underexplored for bladder cancer. We hypothesized that landscape offers insights into immune competency. aimed characterize its dynamics patients with analyze correlations outcomes improve our understanding of response.This study analyzed blood tumor...
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: Patients with high-risk non-muscle invasive bladder cancer (NMIBC) are recommended treatment Bacillus Calmette-Guérin (BCG). The therapeutic effect of BCG is highly dependent on the host immune system and tumor microenvironment (TME). cellular composition functional status TME have been shown to play crucial roles for efficacy. However, much still unknown regarding interactions mechanisms BCG. Using spatial proteomics transcriptomics we investigated cell landscape in a...
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...
BACKGROUND: Morphologically normal tissue, adjacent to tumors, contains multiple molecular changes, the so-called field cancerization. The multifocal and recurrent nature of bladder cancer has been hypothesized originate from this. However, further studies are required explore mutational composition tissue tumors. OBJECTIVE: To analyze cancerization in patients using a non-tumor guided approach. METHODS: We investigated landscape appearing urothelium paired tumors four by applying...
Folates have been shown to play a crucial role for proper development of the embryo as folate deficiency has associated with reduced developmental capacity such increased risk fetal neural tube defects and spontanous abortion. Transcripts encoding carrier RFC1 (SLC19A1 protein) high-affinity receptor FOLR1 are expressed in oocytes preimplantation embryos, respectively. In this study, we observed maternally contributed protein during mouse human ovarian follicle development, 2-cell embryos....
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...
This pre-clinical study was designed to refine a dissection method for validating the use of 15-gene hypoxia classifier, which previously established head and neck squamous cell carcinoma (HNSCC) patients, identify in prostate cancer. PC3 DU-145 adenocarcinoma cells, vitro, were gassed with various oxygen concentrations (0-21%) 24 h, followed by real-time PCR. Xenografts vivo, mice injected hypoxic markers [18F]-FAZA pimonidazole. Subsequently, tumors excised, frozen, cryo-sectioned,...
Abstract Background The functional status of immune cells within the tumor microenvironment and characteristics may explain Bacillus Calmette-Guérin (BCG)-failure in high-risk non-muscle invasive bladder cancer (NMIBC). Objective To characterize molecular correlates BCG-failure using a multiomics approach. Design, Setting, Participants BCG-treated NMIBC patients (n=156) were included. Metachronous tumors analyzed RNA-sequencing (n=170) whole exome sequencing (n=198). Urine samples for...
Abstract Introduction: The recommended treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is intravesical instillations of Bacillus Calmette-Guérin (BCG). However, 40 % experience recurrence within 5 years despite completing BCG treatment. T cell exhaustion has been associated with poor outcome following BCG. Here we investigated if exhaustion, characterized by protein expression PD1 and PD-L1 measured in paired samples obtained before after could further explain response...
Abstract T cells represent essential effector in the intrinsic antitumor immune response. Cancer-specific can recognize cancer neoantigens through their cell receptors (TCRs). The expansion of these clones is believed to be an early response malignancy. We hypothesized that landscape offers insights into competency. aimed characterize TCR repertoire patients with bladder and explore correlations disease outcomes. analyzed a cohort 119 muscle-invasive (MIBC) treated chemotherapy followed by...
Abstract Introduction: Patients with high-risk non-muscle invasive bladder cancer (NMIBC) are recommended treatment Bacillus Calmette-Guérin (BCG). The therapeutic effect of BCG is highly dependent on the host immune system and tumor microenvironment (TME). cellular composition functional status TME have been shown to play crucial roles for efficacy. However, much still unknown regarding interactions mechanisms BCG. Using spatial proteomics transcriptomics, we investigated cell landscape in...
Summary T cells are one of the primary effector in endogenous defense against cancer, yet clinical impact their quantity, diversity, and dynamics remains underexplored. Here we investigated relevance cell receptor (TCR) repertoire patients with bladder cancer. In advanced-stage low pre-treatment peripheral TCR diversity was associated worse overall survival (p=0.024), particularly when it coincided a fraction circulating (p=0.00049). The low-diversity repertoires were dominated by expanded...
Abstract Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the primary treatment for non-muscle-invasive bladder cancer (NMIBC), known to stimulate inflammatory cytokines, notably interferon (IFN)-γ. We observed that prolonged IFN-γ exposure fosters adaptive resistance in recurrent tumors, aiding immune evasion and tumor proliferation. identify HLA-E NKG2A, part of a novel NK T cell checkpoint pathway, as key mediators BCG-unresponsive NMIBC. enhances PD-L1 expression with an enrichment...