IMR Press / FBL / Volume 28 / Issue 10 / DOI: 10.31083/j.fbl2810242
Open Access Original Research
Construction and Validation of a Prognostic Model of Metabolism-Related Genes Driven by Somatic Mutation in Bladder Cancer
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1 Department of Urology, First Hospital of Shanxi Medical University, 030001 Taiyuan, Shanxi, China
2 Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 030032 Taiyuan, Shanxi, China
3 Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China
*Correspondence: tgbz116@126.com (Xiaofeng Yang)
Front. Biosci. (Landmark Ed) 2023, 28(10), 242; https://doi.org/10.31083/j.fbl2810242
Submitted: 30 January 2023 | Revised: 8 May 2023 | Accepted: 18 May 2023 | Published: 19 October 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Metabolic reprogramming is an important player in the prognosis of cancer patients. However, metabolism-related genes (MRGs) that are essential to the prognosis of bladder cancer (BLCA) are nor yet fully understood. The purpose of this study is to use bioinformatics methods to establish prognostic models based on MRGs in BLCA to screen potential biomarkers. Methods: Based on the transcriptomic data from BLCA patients in The Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) databases, we identified the differentially expressed genes related to metabolism and analyzed the functional enrichment by edgeR package. A prognostic model was generated using univariate Cox regression analysis and validated using GEO dataset. The prognostic risk model was analyzed by the Kaplan-Meier curve. The single cell RNA sequencing (scRNA-seq) revealed the gene interaction networks and traced the development trajectories of distinct cell lineages. The levels of key metabolism-related biomarkers in vitro were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Results: We screened 201 differentially expressed metabolism-related genes (DEMRGs), which were significantly enriched in oxidative phosphorylation. The risk model was constructed by 5 biomarkers. qRT-PCR analysis verified that there is a significant higher expression of FASN and MTHFD1L in carcinoma tissue. Conclusions: This study constructed a novel prognostic model based on a combination of clinical and molecular factors that related to metabolic reprogramming, which has the potential to improve the prediction of independent prognosis indicators and management of BLCA patients, leading to better treatment outcomes and survival rates.

Keywords
bladder cancer
metabolism-related genes
somatic mutations
prognostic model
biomarkers
single-cell analysis
Funding
202103021224412/Nature Science Foundation of Shanxi Province
Figures
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