Characteristics, management and survival outcomes in patients with muscle-invasive bladder cancer at high risk of recurrence in France: a subgroup analysis from the coblance cohort.

Purpose: To describe characteristics, management, disease-free survival and overall survival of patients with muscle-invasive bladder cancer (MIBC) at high risk of recurrence (MIBC-HR) undergoing radical cystectomy in France and a subgroup of these patients who did not receive adjuvant chemotherapy after RC and were managed with active surveillance only (MIBC-HR-ASO).

Methods: Patients aged ≥ 18 years with MIBC who had radical cystectomy from October 2012 to June 2018 were identified in the prospective COBLAnCE bladder cancer cohort. Patients with metastatic disease were excluded.

Incidence of Bladder Cancer, Healthcare Pathways, and Economic Burden: A Real-World Observational Study From the French National Healthcare System Database.

Purpose: To assess the incidence (all lesions) of bladder cancer (BC) in France, describe patient characteristics and healthcare pathways during the first year after diagnosis, and estimate medical costs.

Methods: All adult patients with an initial BC diagnosis (ICD-10 codes: C67, D09.0, D41.

A divide-and-conquer approach based on deep learning for long RNA secondary structure prediction: Focus on pseudoknots identification.

The accurate prediction of RNA secondary structure, and pseudoknots in particular, is of great importance in understanding the functions of RNAs since they give insights into their folding in three-dimensional space. However, existing approaches often face computational challenges or lack precision when dealing with long RNA sequences and/or pseudoknots. To address this, we propose a divide-and-conquer method based on deep learning, called DivideFold, for predicting the secondary structures including pseudoknots of long RNAs.

MMnc: multi-modal interpretable representation for non-coding RNA classification and class annotation.

Motivation: As the biological roles and disease implications of non-coding RNAs continue to emerge, the need to thoroughly characterize previously unexplored non-coding RNAs becomes increasingly urgent. These molecules hold potential as biomarkers and therapeutic targets. However, the vast and complex nature of non-coding RNAs data presents a challenge.

Comparison and benchmark of deep learning methods for non-coding RNA classification.

The involvement of non-coding RNAs in biological processes and diseases has made the exploration of their functions crucial. Most non-coding RNAs have yet to be studied, creating the need for methods that can rapidly classify large sets of non-coding RNAs into functional groups, or classes. In recent years, the success of deep learning in various domains led to its application to non-coding RNA classification.

What is a Bladder Cancer Molecular Subtype? - Counterpoint.

In an accompanying paper, Mattias Höglund discusses on what is a bladder cancer molecular subtype. He emphasizes the need to consider the aim of tumor classification, which is obviously critical to the approach. He also focuses on considering primarily the identity features of the neoplastic cells.

HPV DNA Integration at Actionable Cancer-Related Genes Loci in HPV-Associated Carcinomas.

In HPV-associated carcinomas, some examples of cancer-related genes altered by viral insertion and corresponding to potential therapeutic targets have been described, but no quantitative assessment of these events, including poorly recurrent targets, has been reported to date. To document these occurrences, we built and analyzed a database comprised of 1455 cases, including HPV genotypes and tumor localizations. Host DNA sequences targeted by viral integration were classified as "non-recurrent" (one single reported case; 838 loci), "weakly recurrent" (two reported cases; 82 loci), and highly recurrent (≥3 cases; 43 loci).

Cohort profile: COBLAnCE: a French prospective cohort to study prognostic and predictive factors in bladder cancer and to generate real-world data on treatment patterns, resource use and quality of life.

Purpose: Bladder cancer is a complex disease with a wide range of outcomes. Clinicopathological factors only partially explain the variability between patients in prognosis and treatment response. There is a need for large cohorts collecting extensive data and biological samples to: (1) investigate gene-environment interactions, pathological/molecular classification and biomarker discovery; and (2) describe treatment patterns, outcomes, resource use and quality of life in a real-world setting.

Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments.

Purpose: Although there have been improvements in the management of metastatic retinoblastoma, most patients do not survive, and all patients suffer from multiple short- and long-term treatment toxicities. Reliable and informative models to assist clinicians are needed. Thus we developed and comprehensively characterized a novel preclinical platform of primary cell cultures and xenograft models of metastatic retinoblastoma to provide insights into the molecular biology underlying metastases and to perform drug screening for the identification of hit candidates with the highest potential for clinical translation.

Immunohistochemical expression of TFF1 is a marker of poor prognosis in retinoblastoma.

Introduction: The risk of relapse in retinoblastoma is currently determined by the presence of high-risk histopathologic factors in the enucleated eye. However, the probability of developing metastatic disease is heterogeneous among these patients. Evaluating a biological marker to identify high-risk patients could be useful in clinical setting.

A Case-Only Genome-Wide Interaction Study of Smoking and Bladder Cancer Risk: Results from the COBLAnCE Cohort.

Bladder cancer (BC) is the 6th most common cancer worldwide, with tobacco smoking considered as its main risk factor. Accumulating evidence has found associations between genetic variants and the risk of BC. Candidate gene-environment interaction studies have suggested interactions between cigarette smoking and / gene variants.

Transcriptomic Profiling of Upper Tract Urothelial Carcinoma: Bladder Cancer Consensus Classification Relevance, Molecular Heterogeneity, and Differential Immune Signatures.

Analyses of large transcriptomics data sets of muscle-invasive bladder cancer (MIBC) have led to a consensus classification. Molecular subtypes of upper tract urothelial carcinomas (UTUCs) are less known. Our objective was to determine the relevance of the consensus classification in UTUCs by characterizing a novel cohort of surgically treated ≥pT1 tumors.

Germline retrogene insertion in gene involved in cancer predisposition.

About half of the human genome is composed of repeated sequences derived from mobile elements, mainly retrotransposons, generally without pathogenic effect. Familial forms of retinoblastoma are caused by germline pathogenic variants in gene. Here, we describe a family with retinoblastoma affecting a father and his son.

Proteogenomic Characterization of Bladder Cancer Reveals Sensitivity to Apoptosis Induced by Tumor Necrosis Factor-related Apoptosis-inducing Ligand in FGFR3-mutated Tumors.

Background: Molecular understanding of muscle-invasive (MIBC) and non-muscle-invasive (NMIBC) bladder cancer is currently based primarily on transcriptomic and genomic analyses.

Objective: To conduct proteogenomic analyses to gain insights into bladder cancer (BC) heterogeneity and identify underlying processes specific to tumor subgroups and therapeutic outcomes.

Design, Setting, And Participants: Proteomic data were obtained for 40 MIBC and 23 NMIBC cases for which transcriptomic and genomic data were already available.

Epigenomic mapping identifies an enhancer repertoire that regulates cell identity in bladder cancer through distinct transcription factor networks.

Muscle-invasive bladder cancer (BLCA) is an aggressive disease. Consensus BLCA transcriptomic subtypes have been proposed, with two major Luminal and Basal subgroups, presenting distinct molecular and clinical characteristics. However, how these distinct subtypes are regulated remains unclear.

Prognostic impact of variant histologies in urothelial bladder cancer treated with radical cystectomy.

Objectives: To evaluate variant histologies (VHs) for disease-specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC).

Materials And Methods: We analysed a multi-institutional cohort of 1082 patients treated with upfront RC for cT1-4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox' regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage-based analyses.

Transcription factor EB regulates phosphatidylinositol-3-phosphate levels that control lysosome positioning in the bladder cancer model.

Lysosomes orchestrate degradation and recycling of exogenous and endogenous material thus controlling cellular homeostasis. Little is known how this organelle changes during cancer. Here we investigate the intracellular landscape of lysosomes in a cellular model of bladder cancer.

Progression-associated molecular changes in basal/squamous and sarcomatoid bladder carcinogenesis.

The aggressive basal/squamous (Ba/Sq) bladder cancer (BLCA) subtype is often diagnosed at the muscle-invasive stage and can progress to the sarcomatoid variant. Identification of molecular changes occurring during progression from non-muscle-invasive BLCA (NMIBC) to Ba/Sq muscle-invasive BLCA (MIBC) is thus challenging in human disease. We used the N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) mouse model of Ba/Sq MIBC to study longitudinally the molecular changes leading to the Ba/Sq phenotype and to the sarcomatoid variant using IHC and microdissection followed by RNA-seq at all stages of progression.

FGFR3 Mutational Activation Can Induce Luminal-like Papillary Bladder Tumor Formation and Favors a Male Sex Bias.

Background: Bladder cancer (BCa) is more common in men and presents differences in molecular subtypes based on sex. Fibroblast growth factor receptor 3 (FGFR3) mutations are enriched in the luminal papillary muscle-invasive BCa (MIBC) and non-MIBC subtypes.

Objective: To determine whether FGFR3 mutations initiate BCa and impact BCa male sex bias.

Follow-up of intraocular retinoblastoma through the quantitative analysis of conserved nuclear DNA sequences in aqueous humor from patients.

Fundoscopy is the standard method for diagnosis and follow-up of intraocular retinoblastoma, but it is sometimes insufficient to discern whether tumors are inactivated following treatments. In this work, we hypothesized that the amount of conserved nuclear DNA sequences in the cell-free DNA (cfDNA) fraction of the aqueous humor (AH) might complement fundoscopy for retinoblastoma follow-up. To address our hypothesis, we developed highly sensitive droplet digital polymerase chain reaction (ddPCR) methods to quantify highly conserved DNA sequences of nucleus-encoded genes (GAPDH and B4GALNT1) and of a mitochondrial gene, MT-ATP6.

Integrated molecular and pharmacological characterization of patient-derived xenografts from bladder and ureteral cancers identifies new potential therapies.

Background: Muscle-invasive bladder cancer (MIBC) and upper urinary tract urothelial carcinoma (UTUC) are molecularly heterogeneous. Despite chemotherapies, immunotherapies, or anti-fibroblast growth factor receptor (FGFR) treatments, these tumors are still of a poor outcome. Our objective was to develop a bank of patient-derived xenografts (PDXs) recapitulating the molecular heterogeneity of MIBC and UTUC, to facilitate the preclinical identification of therapies.

Tyro3 Targeting as a Radiosensitizing Strategy in Bladder Cancer through Cell Cycle Dysregulation.

Bladder cancer is a common cancer; it is the tenth most common cancer in the world. Around one fourth of all diagnosed patients have muscle-invasive bladder cancer (MIBC), characterized by advanced tumors and which remains a lethal disease. The standard treatment for MIBC is the bladder removal by surgery.

Identification of immunosuppressive factors in retinoblastoma cell secretomes and aqueous humor from patients.

The microenvironment of retinoblastoma, the solid malignancy of the developing retina, is immunosuppressive. To study the interactions between tumor-associated microglia/macrophages (TAMs) and tumor cells in retinoblastomas, we analyzed immunohistochemistry markers in 23 patient samples and characterized 105 secreted cytokines of 11 retinoblastoma cell models in culture. We detected profuse infiltration of CD163 protumoral M2-like polarized TAMs in eyes enucleated due to cancer progression.