Identification and validation of prognostic signature genes of bladder cancer by integrating methylation and transcriptomic analysis

Being a frequent malignant tumor of the genitourinary system, Bladder Urothelial Carcinoma (BLCA) has a poor prognosis. This study focused on identifying and validating prognostic biomarkers utilizing methylation, transcriptomics, and clinical data from The Cancer Genome Atlas Bladder Urothelial Car...

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Bibliographic Details
Published in:Scientific reports 2024-01, Vol.14 (1), p.368-368, Article 368
Main Authors: Chatterjee, Dipankor, Mou, Sadia Islam, Sultana, Tamanna, Hosen, Md. Ismail, Faruk, Md. Omar
Format: Article
Language:English
Subjects:
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ADP-ribosylation
ADP-ribosylation factor
Bladder cancer
Carcinoma, Transitional Cell
Carrier Proteins
DNA methylation
Epidermal growth factor receptors
Fos-related antigen
Gene Expression Profiling
Genes
Genomes
Humanities and Social Sciences
Humans
Immune response
Medical prognosis
Methylation
multidisciplinary
Oncogene Proteins
Precision medicine
Prognosis
Risk groups
Science
Science (multidisciplinary)
Survival analysis
Transcriptomics
Tumor Microenvironment
Tumors
Urinary Bladder Neoplasms - genetics
Urothelial cancer
Urothelial carcinoma
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Summary:Being a frequent malignant tumor of the genitourinary system, Bladder Urothelial Carcinoma (BLCA) has a poor prognosis. This study focused on identifying and validating prognostic biomarkers utilizing methylation, transcriptomics, and clinical data from The Cancer Genome Atlas Bladder Urothelial Carcinoma (TCGA BLCA) cohort. The impact of altered differentially methylated hallmark pathway genes was subjected to clustering analysis to observe changes in the transcriptional landscape on BLCA patients and identify two subtypes of patients from the TCGA BLCA population where Subtype 2 was associated with the worst prognosis with a p -value of 0.00032. Differential expression and enrichment analysis showed that subtype 2 was enriched in immune-responsive and cancer-progressive pathways, whereas subtype 1 was enriched in biosynthetic pathways. Following, regression and network analyses revealed Epidermal Growth Factor Receptor (EGFR), Fos-related antigen 1 (FOSL1), Nuclear Factor Erythroid 2 (NFE2), ADP-ribosylation factor-like protein 4D (ARL4D), SH3 domain containing ring finger 2 (SH3RF2), and Cadherin 3 (CDH3) genes to be the most significant prognostic gene markers. These genes were used to construct a risk model that separated the BLCA patients into high and low-risk groups. The risk model was also validated in an external dataset by performing survival analysis between high and low-risk groups with a p -value 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-50740-x