Unveiling the Role of DPYS: A New Prognostic Biomarker in Sarcoma.

IF 1.9 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current protein & peptide science Pub Date : 2025-04-04 DOI:10.2174/0113892037362065250227064739

Guizhen Lyu, Dongbing Li

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引用次数: 0

Abstract

Background: Dihydropyrimidinase (DPYS), a pivotal enzyme in the pyrimidine synthesis pathway, has been increasingly studied for its potential role in cancer therapy. While its presence has been noted in various cancers, its specific impact on sarcoma (SARC) still needs to be fully understood.

Objective: This study sought to explore the correlation between DPYS expression and SARC, utilizing data from The Cancer Genome Atlas (TCGA), bioinformatics tools, and experimental validation.

Methods: The study employed statistical analysis and logistic regression to assess the link between DPYS expression levels and clinical features in SARC patients. Survival analysis was conducted using the Kaplan-Meier method and Cox regression, evaluating the prognostic significance of DPYS expression. Gene set enrichment analysis and immuno-infiltration analysis were conducted to uncover the potential regulatory mechanisms of the DPYS gene. We validated the expression of DPYS using GSE17674. Quantitative reverse transcription PCR was utilized to measure DPYS expression levels in SARC cell lines.

Results: The study found that reduced DPYS expression in SARC correlated with therapeutic response (P = 0.011), histological subtype (P = 0.003), and the presence of residual tumor (P = 0.043). Reduced DPYS expression was a predictor of inferior Overall Survival (OS), with a Hazard Ratio (HR) of 0.56 and a 95% Confidence Interval (CI) of 0.37-0.84 (P = 0.005), as well as Disease-Specific Survival (DSS), with an HR of 0.64 and a 95% CI of 0.41-1.00 (P = 0.048). DPYS expression was also identified as an independent factor for OS in SARC (HR: 0.335; 95% CI: 0.169-0.664; P = 0.002). The gene was associated with various pathways, including GPCR ligand binding, signaling by interleukins, G alpha (i) signaling events, Class A/1 Rhodopsin-like receptors, cytokine-cytokine receptor interaction, and platelet activation. DPYS expression also showed a correlation with certain immune cell infiltrates and was found to be significantly downregulated in SARC cell lines.

Conclusion: DPYS may serve as a potential prognostic biomarker and therapeutic target for SARC.

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来源期刊

Current protein & peptide science 生物-生化与分子生物学

CiteScore

5.20

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Current Protein & Peptide Science publishes full-length/mini review articles on specific aspects involving proteins, peptides, and interactions between the enzymes, the binding interactions of hormones and their receptors; the properties of transcription factors and other molecules that regulate gene expression; the reactions leading to the immune response; the process of signal transduction; the structure and function of proteins involved in the cytoskeleton and molecular motors; the properties of membrane channels and transporters; and the generation and storage of metabolic energy. In addition, reviews of experimental studies of protein folding and design are given special emphasis. Manuscripts submitted to Current Protein and Peptide Science should cover a field by discussing research from the leading laboratories in a field and should pose questions for future studies. Original papers, research articles and letter articles/short communications are not considered for publication in Current Protein & Peptide Science.