Whole-exome sequencing of paired tumour/blood of 58 T1 stage bladder cancer patients
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ABSTRACT:
PROVIDER: EGAS00001005765 | EGA |
REPOSITORIES: EGA
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Project description:Stage T1 bladder cancer presents a high risk of progression and requires improved understanding. In continuation of our whole-exome sequencing study on this subtype of the disease, we carried out this targeted paired tumour/blood sequencing study including 34 T1 stage bladder cancer patients. Agilent’s SureDesign tool was used to design a 1.133 Mb SureSelect custom capture for all coding exons of the 140 selected candidate genes.
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Project description:Background: Intravesical bacillus Calmette-Guérin (BCG) therapy is standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) but overall efficacy is low, and no reliable predictive biomarkers currently exist to refine patient selection. We performed genomic analysis on high-grade (HG) T1 NMIBCs to determine if response to therapy is predicted by certain mutational and/or expressional changes. Methods: Patients with HG T1 NMIBC treated with induction BCG were stratified by response into durable and non-durable responders. Tumor samples were subjected to whole-exome RNA sequencing. Gene expression and variant analysis were performed on RNA sequencing to identify changes between BCG durable responders and those that did not respond. Results: Differentially expressed genes in durable responders were input into IPA and identified associated immune related pathways: MIF-mediated Glucocorticoid Regulation, MIF Regulation of Innate Immunity, and p38 MAPK Signaling. The differentially expressed genes were crossed with RNAseq variant analysis to identify genes that had significant changes in both. This analysis identified JCHAIN, S100A7, CLECB, and ANXA10 genes that had snps in non-durable responders vs durable responders and also had significant change in gene expression between these two groups. Conclusions: Differences in the genomic profiles of HG T1 NMIBC tumors exist between those who show durable response to BCG and those who do not. Using pathway analysis, those differences imply upregulation of several interconnected inflammatory pathways among responders. Specific variants identified here are candidates for further study and, if clinically validated, may serve as useful biomarkers in the future.
2021-06-05 | GSE176178 | GEO
Project description:miRNAs are involved in cancer development and progression,acting as tumor suppressors or oncogenes. Half of the human miRNAs are located in cancer-associated genomic regions and can function as tumor suppressor genes or oncogenes depending on their targets miRNA profiling was performed on paired bladder cancer tissues and differentially expressed miRNAs were identified in BC and adjacent noncancerous tissues of any disease stage/grade. Ten paired bladder cancer tissues (5 low-grade non-muscle-invasive bladder cancer[NMIBC] and 5 high-grade muscle-invasive bladder cancer[MIBC]) were sent to CapitalBio Corp. (Beijing) for noncoding RNA microarray analysis. The microarray analysis was done as described on the Web site of CapitalBio. NMIBC samples include 07A, 19A, 23A, 24A and T63 while coresponding pairs include 07B, 19B, 23B, 24B and 63. MIBC samples include 10A, 20A, 21A, 34A and 49A while coresponding pairs include 10B, 20B, 21B, 34B and 49B.
2012-07-06 | E-GEOD-39093 | biostudies-arrayexpress
Project description:We present the first computational approach to reconstruct the sequence of copy number alterations driving carcinogenesis from the analysis of several tumor samples of a same patient. Applied to BAC array-CGH and SNP array data from bladder and breast cancers, this method proved highly valuable to establish the clonal relationships between primary tumors and recurrences and to identify the chromosome aberrations at the initiation of tumorigenesis. Keywords: Comparative Genomic Hybridization An algorithm was developed to reconstruct tumors lineage and the sequence of copy number alterations along tumorigenesis from the analysis of several samples from a same patient. The data here consist in CGH data from 58 bladder tumors. 50 of these tumors come from independent samples and were used to compute the frequencies of breakpoints at each location. The 8 other samples (S1_A, S1_B, S2_A, S2_B, S3_A, S3_B, S3_C and S3_D) are multiple tumors from 3 patients. They were used to reconstruct the sequence of chromosome aberrations along cancer development in these 3 patients.
2010-05-19 | E-GEOD-19193 | biostudies-arrayexpress
Project description:Bladder tumours used to construct a tumour stage classifier Keywords = bladder cancer, disease stages, classification Keywords: other
2002-12-08 | GSE89 | GEO
Project description:Stage T1 bladder cancers have the highest progression and recurrence rates of all non-muscle invasive bladder tumors. T1 tumors are heterogeneous; while most T1 patients are treated with BCG, many will progress and die from bladder cancer, and particularly aggressive tumors could be treated by early cystectomy. To better understand the molecular heterogeneity of T1 cancers, we performed transcriptome profiling and unsupervised clustering, identifying five consensus subtypes of T1 tumors treated with reTUR, induction and maintenance BCG. The T1-LumGU subtype was associated with CIS (6/13, 46% of all CIS), had high E2F1 and EZH2 expression, and enriched E2F target and G2M checkpoint Hallmarks. T1-Inflam was inflamed and infiltrated with immune cells. While most T1 tumors were classified as luminal papillary, the T1-TLum subtype had the highest median Luminal Papillary score and FGFR3 expression, no recurrence events, and the fewest copy number gains. T1-Myc and T1-Early subtypes had the most recurrences (14/30 within 24 months), highest median MYC expression, and, when combined, had significantly worse recurrence-free survival than the other three subtypes. T1-Early had 5 (38%) recurrences within the first 6 months of BCG, and repressed IFN-alpha and IFN-gamma Hallmarks and inflammation. We developed a single-patient T1 classifier and validated our subtype biology in a second cohort of T1 tumors. Future research will be necessary to validate the proposed T1 subtypes and to determine if therapies can be individualized for each subtype.
2020-07-13 | GSE154261 | GEO
Project description:Tumor-blood paired whole-exome sequencing of 58 pairs of non-muscle-invasive bladder cancer samples (stageT1). Targeted sequencing of 112 non-muscle-invasive bladder cancer samples (34 stage T1; 78 stage Ta)
| EGAD00001008332 | EGA