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Immune profiles and DNA methylation alterations related to non-muscle-invasive bladder cancer outcomes

ABSTRACT: Immune profiles and DNA methylation alterations related to non-muscle-invasive bladder cancer outcomes

PROVIDER: PRJNA762866 | ENA |

REPOSITORIES: ENA

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Immune profiles and DNA methylation alterations related to non-muscle-invasive bladder cancer outcomes

Project description:Non-muscle-invasive bladder cancer (NMIBC) patients receive frequent monitoring because ≥ 70% will have recurrent disease. However, screening is invasive, expensive, and associated with significant morbidity making bladder cancer the most expensive cancer to treat per capita. There is an urgent need to expand the understanding of markers related to recurrence and survival outcomes of NMIBC. Our results expand on the knowledge of immune profiles and methylation alteration associated with NMIBC outcomes and represent a first step toward the development of DNA methylation-based biomarkers of tumor recurrence.

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Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer

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Comparison of gene expression profiling of human non-muscle invasive bladder cancer and muscle invasive bladder cancer

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Urinary Glycoproteomic profiling of Non-Muscle Invasive and Muscle Invasive Bladder Carcinoma Patients reveals distinct N-glycosylation pattern of CD44, MGAM and GINM1

Project description:Clinical management of bladder carcinomas (BC) remains a major challenge and demands comprehensive multi-omics analysis for better stratification of the disease. Identification of patients on risk requires identification of signatures predicting prognosis risk of the patients. Understanding the molecular alterations associated with the disease onset and progression could improve the routinely used diagnostic and therapy procedures. In this study, we investigated the aberrant changes in N-glycosylation pattern of proteins associated with tumorigenesis as well as disease progression in bladder cancer. We integrated and compared global N-glycoproteomic and proteomic profile of urine samples from bladder cancer patients at different clinicopathological stages (non-muscle invasive and muscle-invasive patients (n=5 and 4 in each cohort)) with healthy subjects (n=5) using SPEG method. We identified 635 N-glycopeptides corresponding to 381 proteins and 543 N-glycopeptides corresponding to 326 proteins in NMIBC and MIBC patients respectively. Moreover, we identified altered glycosylation in 41 NMIBC and 21 MIBC proteins without any significant change in protein abundance levels. In concordance with the previously published bladder cancer cell line N-glycoproteomic data, we also observed dysregulated glycosylation in ECM related proteins. Further, we identified distinct N-glycosylation pattern of CD44, MGAM and GINM1 between NMIBC and MIBC patients, which may be associated with disease progression in bladder cancer. These aberrant protein glycosylation events would provide a novel approach for bladder carcinoma diagnosis and further define novel mechanisms of tumor initiation and progression.

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Project description:This RNA-sequencing cohort includes 52 Non-muscle Invasive Bladder cancer (NMIBC) samples and 6 Muscle Invasive Bladder cancer (MIBC) samples.

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Divergent biological response to neoadjuvant chemotherapy in muscle-invasive bladder cancer

Project description:Despite cisplatin-based neoadjuvant chemotherapy (NAC) 60% of patients with muscle-invasive bladder cancer still have residual invasive disease at radical cystectomy (RC). The NAC-induced biological alterations in these cisplatin-resistant tumors remain largely unstudied. We analyzed gene expression from 133 patients with residual invasive disease after cisplatin-based NAC. H&E and immunohistochemistry were used to confirm tissue sampling and gene expression analysis. Established molecular subtyping models proved to be inconsistent in their classification of the post-NAC samples. Unsupervised consensus clustering revealed four distinct consensus clusters (CC). The CC1-Basal and CC2-Luminal subtypes expressed genes consistent with a basal-like and a luminal-like phenotype, respectively. The CC3-Immune subtype had the highest immune activity, including T-cell infiltration and checkpoint molecule expression, but lacked both basal and luminal markers. The CC4-Scar-like subtype expressed genes associated with wound-healing/ scarring and was associated with favorable prognosis.

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