A transcriptome study of p53-pathway related prognostic gene signature set in bladder cancer
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
Affiliations
Safayat Mahmud Khan
Clinical Biochemistry and Translational Medicine Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh
Tonmoy Das
Systems Cell-Signalling Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh
Sajib Chakraborty
Systems Cell-Signalling Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh
Abdul Matin Anamur Rashid Choudhury
Department. Uro-Oncology, National Institute of Cancer Research Hospital, Bangladesh
Howlader Fazlul Karim
Department. Uro-Oncology, National Institute of Cancer Research Hospital, Bangladesh
Munshi Akid Mostofa
Department. Uro-Oncology, National Institute of Cancer Research Hospital, Bangladesh
Hasib Uddin Ahmed
Clinical Biochemistry and Translational Medicine Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh
Md Akmal Hossain
Clinical Biochemistry and Translational Medicine Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh
Florence Le Calvez-Kelm
Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC), 69372, Lyon, France
Md Ismail Hosen
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.
Hossain Uddin Shekhar
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.
