A transcriptome study of p53-pathway related prognostic gene signature set in bladder cancer
p53 pathway is important in tumorigenesis. However, no study has been performed to specifically investigate the role of p53 pathway genes in bladder cancer (BLCA). In this study, transcriptomics data of muscle invasive bladder cancer patients (n = 411) from The Cancer Genome Atlas (TCGA) were invest...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-10-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402308266X |
| _version_ | 1797646467056271360 |
|---|---|
| author | Safayat Mahmud Khan Tonmoy Das Sajib Chakraborty Abdul Matin Anamur Rashid Choudhury Howlader Fazlul Karim Munshi Akid Mostofa Hasib Uddin Ahmed Md Akmal Hossain Florence Le Calvez-Kelm Md Ismail Hosen Hossain Uddin Shekhar |
| author_facet | Safayat Mahmud Khan Tonmoy Das Sajib Chakraborty Abdul Matin Anamur Rashid Choudhury Howlader Fazlul Karim Munshi Akid Mostofa Hasib Uddin Ahmed Md Akmal Hossain Florence Le Calvez-Kelm Md Ismail Hosen Hossain Uddin Shekhar |
| author_sort | Safayat Mahmud Khan |
| collection | DOAJ |
| description | p53 pathway is important in tumorigenesis. However, no study has been performed to specifically investigate the role of p53 pathway genes in bladder cancer (BLCA). In this study, transcriptomics data of muscle invasive bladder cancer patients (n = 411) from The Cancer Genome Atlas (TCGA) were investigated. Using the hallmark p53 pathway gene set, the Non-Negative Matrix factorization (NMF) analysis identified two subtypes (C1 and C2). Clinical, survival, and immunological analysis were done to validate distinct characteristics of the subtypes. Pathway enrichment analysis showed the subtype C1 with poor prognosis having enrichment in genes of the immunity related pathways, where C2 subtype with better prognosis being enriched in genes of the steroid synthesis and drug metabolism pathways. A signature gene set consisting of MDGA2, GNLY, GGT2, UGT2B4, DLX1, and DSC1 was created followed by a risk model. Their expressions were analyzed in RNA extracted from the blood and matched tumor tissues of BLCA patients (n = 10). DSC1 had significant difference of expression (p = 0.005) between the blood and tumor tissues in our BLCA samples. Contrary to the usual normal bladder tissue to blood ratio, DLX1 expression was lower (p = 0.02734) in tumor tissues than in blood. Being the first research of p53 pathway related signature gene set in bladder cancer, this study potentially has a substantial impact on the development of biomarkers for BLCA. |
| first_indexed | 2024-03-11T15:02:00Z |
| format | Article |
| id | doaj.art-a6819b5781694251b4b91873fb91669f |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-11T15:02:00Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-a6819b5781694251b4b91873fb91669f2023-10-30T06:08:15ZengElsevierHeliyon2405-84402023-10-01910e21058A transcriptome study of p53-pathway related prognostic gene signature set in bladder cancerSafayat Mahmud Khan0Tonmoy Das1Sajib Chakraborty2Abdul Matin Anamur Rashid Choudhury3Howlader Fazlul Karim4Munshi Akid Mostofa5Hasib Uddin Ahmed6Md Akmal Hossain7Florence Le Calvez-Kelm8Md Ismail Hosen9Hossain Uddin Shekhar10Clinical Biochemistry and Translational Medicine Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, BangladeshSystems Cell-Signalling Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, BangladeshSystems Cell-Signalling Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, BangladeshDepartment. Uro-Oncology, National Institute of Cancer Research Hospital, BangladeshDepartment. Uro-Oncology, National Institute of Cancer Research Hospital, BangladeshDepartment. Uro-Oncology, National Institute of Cancer Research Hospital, BangladeshClinical Biochemistry and Translational Medicine Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, BangladeshClinical Biochemistry and Translational Medicine Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, BangladeshGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC), 69372, Lyon, FranceClinical Biochemistry and Translational Medicine Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh; Corresponding author. Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.Clinical Biochemistry and Translational Medicine Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh; Corresponding author. Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh.p53 pathway is important in tumorigenesis. However, no study has been performed to specifically investigate the role of p53 pathway genes in bladder cancer (BLCA). In this study, transcriptomics data of muscle invasive bladder cancer patients (n = 411) from The Cancer Genome Atlas (TCGA) were investigated. Using the hallmark p53 pathway gene set, the Non-Negative Matrix factorization (NMF) analysis identified two subtypes (C1 and C2). Clinical, survival, and immunological analysis were done to validate distinct characteristics of the subtypes. Pathway enrichment analysis showed the subtype C1 with poor prognosis having enrichment in genes of the immunity related pathways, where C2 subtype with better prognosis being enriched in genes of the steroid synthesis and drug metabolism pathways. A signature gene set consisting of MDGA2, GNLY, GGT2, UGT2B4, DLX1, and DSC1 was created followed by a risk model. Their expressions were analyzed in RNA extracted from the blood and matched tumor tissues of BLCA patients (n = 10). DSC1 had significant difference of expression (p = 0.005) between the blood and tumor tissues in our BLCA samples. Contrary to the usual normal bladder tissue to blood ratio, DLX1 expression was lower (p = 0.02734) in tumor tissues than in blood. Being the first research of p53 pathway related signature gene set in bladder cancer, this study potentially has a substantial impact on the development of biomarkers for BLCA.http://www.sciencedirect.com/science/article/pii/S240584402308266XNMFBLCAp53BiomarkerEnrichmentTCGA |
| spellingShingle | Safayat Mahmud Khan Tonmoy Das Sajib Chakraborty Abdul Matin Anamur Rashid Choudhury Howlader Fazlul Karim Munshi Akid Mostofa Hasib Uddin Ahmed Md Akmal Hossain Florence Le Calvez-Kelm Md Ismail Hosen Hossain Uddin Shekhar A transcriptome study of p53-pathway related prognostic gene signature set in bladder cancer Heliyon NMF BLCA p53 Biomarker Enrichment TCGA |
| title | A transcriptome study of p53-pathway related prognostic gene signature set in bladder cancer |
| title_full | A transcriptome study of p53-pathway related prognostic gene signature set in bladder cancer |
| title_fullStr | A transcriptome study of p53-pathway related prognostic gene signature set in bladder cancer |
| title_full_unstemmed | A transcriptome study of p53-pathway related prognostic gene signature set in bladder cancer |
| title_short | A transcriptome study of p53-pathway related prognostic gene signature set in bladder cancer |
| title_sort | transcriptome study of p53 pathway related prognostic gene signature set in bladder cancer |
| topic | NMF BLCA p53 Biomarker Enrichment TCGA |
| url | http://www.sciencedirect.com/science/article/pii/S240584402308266X |
| work_keys_str_mv | AT safayatmahmudkhan atranscriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT tonmoydas atranscriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT sajibchakraborty atranscriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT abdulmatinanamurrashidchoudhury atranscriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT howladerfazlulkarim atranscriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT munshiakidmostofa atranscriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT hasibuddinahmed atranscriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT mdakmalhossain atranscriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT florencelecalvezkelm atranscriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT mdismailhosen atranscriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT hossainuddinshekhar atranscriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT safayatmahmudkhan transcriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT tonmoydas transcriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT sajibchakraborty transcriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT abdulmatinanamurrashidchoudhury transcriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT howladerfazlulkarim transcriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT munshiakidmostofa transcriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT hasibuddinahmed transcriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT mdakmalhossain transcriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT florencelecalvezkelm transcriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT mdismailhosen transcriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer AT hossainuddinshekhar transcriptomestudyofp53pathwayrelatedprognosticgenesignaturesetinbladdercancer |