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

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.

Keywords: GPCR ligand binding; Sarcoma; dihydropyrimidinase; immune infiltrates; prognosis; therapeutic target..