Comprehensive genomic characterization of early-stage bladder cancer.

Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes.

Multiomics profiling of urothelial carcinoma reveals CIS-specific gene signature and immune characteristics.

Urothelial carcinoma (CIS) is an aggressive phenotype of non-muscle-invasive bladder cancer. Molecular features unique to CIS compared to high-grade papillary tumors are underexplored. RNA sequencing of CIS, papillary tumors, and normal urothelium showed lower immune marker expression in CIS compared to papillary tumors.

Field Cancerization Is Associated with Tumor Development, T-cell Exhaustion, and Clinical Outcomes in Bladder Cancer.

Background: Field cancerization is characterized by areas of normal tissue affected by mutated clones. Bladder field cancerization may explain the development and recurrence of bladder cancer and may be associated with treatment outcomes.

Objective: To investigate the predictive and prognostic roles of field cancerization in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with bacillus Calmette-Guérin (BCG).

Single-nucleus and Spatially Resolved Intratumor Subtype Heterogeneity in Bladder Cancer.

Background: Current bulk transcriptomic classification systems for bladder cancer do not consider the level of intratumor subtype heterogeneity.

Objective: To investigate the extent and possible clinical impact of intratumor subtype heterogeneity across early and more advanced stages of bladder cancer.

Design Setting And Participants: We performed single-nucleus RNA sequencing (RNA-seq) of 48 bladder tumors and additional spatial transcriptomics for four of these tumors.

Cell-Free Urine and Plasma DNA Mutational Analysis Predicts Neoadjuvant Chemotherapy Response and Outcome in Patients with Muscle-Invasive Bladder Cancer.

Purpose: To investigate the use of plasma and urine DNA mutation analysis for predicting neoadjuvant chemotherapy (NAC) response and oncological outcome in patients with muscle-invasive bladder cancer.

Experimental Design: Whole-exome sequencing of tumor and germline DNA was performed for 92 patients treated with NAC followed by radical cystectomy (RC). A custom NGS-panel capturing approximately 50 mutations per patient was designed and used to track mutated tumor DNA in plasma and urine.

Elevated T-cell Exhaustion and Urinary Tumor DNA Levels Are Associated with Bacillus Calmette-Guérin Failure in Patients with Non-muscle-invasive Bladder Cancer.

Background: The functional status of immune cells in the tumor microenvironment and tumor characteristics may explain bacillus Calmette-Guérin (BCG) failure in high-risk non-muscle-invasive bladder cancer (NMIBC).

Objective: To characterize molecular correlates of post-BCG high-grade (HG) recurrence using multiomics analysis.

Design, Setting, And Participants: Patients with BCG-treated NMIBC (n = 156) were included in the study.

Refinement of an Established Procedure and Its Application for Identification of Hypoxia in Prostate Cancer Xenografts.

Background: This pre-clinical study was designed to refine a dissection method for validating the use of a 15-gene hypoxia classifier, which was previously established for head and neck squamous cell carcinoma (HNSCC) patients, to identify hypoxia in prostate cancer.

Methods: PC3 and DU-145 adenocarcinoma cells, in vitro, were gassed with various oxygen concentrations (0-21%) for 24 h, followed by real-time PCR. Xenografts were established in vivo, and the mice were injected with the hypoxic markers [18F]-FAZA and pimonidazole.

An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer.

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 with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness.

Maternally Contributed Folate Receptor 1 Is Expressed in Ovarian Follicles and Contributes to Preimplantation Development.

Folates have been shown to play a crucial role for proper development of the embryo as folate deficiency has been associated with reduced developmental capacity such as increased risk of fetal neural tube defects and spontanous abortion. Transcripts encoding the reduced folate carrier RFC1 (SLC19A1 protein) and the high-affinity folate receptor FOLR1 are expressed in oocytes and preimplantation embryos, respectively. In this study, we observed maternally contributed FOLR1 protein during mouse and human ovarian follicle development, and 2-cell mouse embryos.