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Gene expression in muscle invasive and non-muscle invasive bladder cancer cell lines exposed to hypoxia

ABSTRACT: Gene expression in muscle invasive and non-muscle invasive bladder cancer cell lines exposed to hypoxia

PROVIDER: PRJNA1291182 | ENA |

REPOSITORIES: ENA

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Gene expression in muscle invasive and non-muscle invasive bladder cancer cell lines exposed to hypoxia

Project description:Introductionon: Hypoxic cancers are radioresistant, but biomarkers based on expression of multiple genes can identify patients who will benefit from hypoxia modification. Most studies identifying relevant genes exposed cells in culture to 1% oxygen, which activates hypoxia-inducible factor (HIF). However, oxygen concentrations in hypoxic tumours are heterogeneous ranging from <0.1%. As lower oxygen levels would likely affect transcriptional responses, we aimed to investigate how gene selection at different oxygen levels affects the genes identified and their prognostic capability. Methods: Four MIBC (J82, T24, UMUC3, HT1376) and two non-MIBC (RT4, RT112) bladder cancer cell lines were exposed to varying oxygen levels (20%, 1%, 0.2% and 0.1% O2) for 24 h then harvested and frozen. RNA was extracted and transcriptomes analysed using Clariom S microarrays. Differences in gene expression were investigated. Prognostic and predictive significance of a published 24-gene signature was compared with one generated from genes identified at lower oxygen levels.

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RNA-sequencing of Non-muscle Invasive Bladder cancer (NMIBC)

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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Expression profile of non-muscle invasive (superficial) bladder carcinoma

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

Project description:The biological behaviors, clinical treatment, prognosis of nonmuscle-invasive bladder cancers (NMIBCs) and muscle-invasive bladder cancers (MIBCs) are distinct. Therefore, we performed high-through microarray screening of mRNA expression in 30 bladder tumors, to filter out some of the differential expression genes in NMIBCs and MIBCs.A total of 11 Genes in MIBCs versus in NMIBCs were considered differentially transcribed if they were transcribed ≤2.0 fold change and p<0.001 by unpaired T-test, including 9 up-regulated genes and 2 down-regulated genes in MIBCs (NR4A2, PLK3, CYR61, APOLD1, C13ORF33, LIG4, RBMS3, PCK2, AK098422, HSD17B3, RTN4). These candidate genes were validated in further and provide further insight into the discovery of new putative markers to identify MIBCs preoperatively.

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FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer

Project description:Identification of transcriptional regulatory networks in muscle invasive and non-muscle invasive bladder cancer cell lines

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Recurrence in non-muscle invasive bladder cancer

Project description:Although non muscle-invasive bladder cancer can be treated successfully by surgical resection, there is a high rate of recurrence, which frequently develops into an invasive form of cancer. Due to the lack of marker molecules to predict recurrence, it is currently recommended that after resection each patient is screened via cystoscopy at least twice a year. This results in a psychic burden to the patient and substantial economic costs to the health care system. Using antibody microarrays targeting 724 different cancer-related proteins, we studied protein profiles of patients with and without recurrence. The analysis revealed 255 proteins of differential abundance. Most are involved in the regulation and execution of apoptosis and cell proliferation. For prognosis, a signature of 20 proteins was determined that predicts bladder cancer recurrence with 100% sensitivity and 80% specificity. As a measure of overall accuracy, the area under the curve (AUC) value was found to be 90%. This is well within a clinically relevant window of quality and should support decision making about the stringency of surveillance or even different treatment options.

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RNA-seq profiling identifies lncRNAs in serum as potential biomarker for muscle-invasive bladder cancer

Project description:To investigate the expression profiles of lncRNAs in muscle-invasive bladder cancer .

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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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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.

2020-09-10 | PXD020078 | Pride

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