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

IF 1.9 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
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.

揭示ddpys的作用:一种新的肉瘤预后生物标志物。
背景:二氢嘧啶酶(Dihydropyrimidinase, DPYS)是嘧啶合成途径中的关键酶,因其在癌症治疗中的潜在作用而受到越来越多的研究。虽然它存在于各种癌症中,但它对肉瘤(SARC)的具体影响仍需充分了解。目的:本研究利用癌症基因组图谱(TCGA)、生物信息学工具和实验验证的数据,探讨ddpys表达与SARC的相关性。方法:采用统计学分析和logistic回归分析方法,探讨ddpys表达水平与SARC患者临床特征的关系。采用Kaplan-Meier法和Cox回归进行生存分析,评价DPYS表达对预后的意义。通过基因集富集分析和免疫浸润分析揭示DPYS基因的潜在调控机制。我们使用GSE17674验证DPYS的表达。采用定量反转录PCR法检测ddpys在SARC细胞株中的表达水平。结果:研究发现,ddpys在SARC中表达降低与治疗效果(P = 0.011)、组织学亚型(P = 0.003)、是否存在肿瘤残留(P = 0.043)相关。ddpys表达降低是总生存期(OS)较差的预测因子,风险比(HR)为0.56,95%可信区间(CI)为0.37-0.84 (P = 0.005),疾病特异性生存期(DSS)为0.64,95% CI为0.41-1.00 (P = 0.048)。ddpys表达也被确定为SARC OS的独立因素(HR: 0.335;95% ci: 0.169-0.664;P = 0.002)。该基因与多种途径相关,包括GPCR配体结合、白介素信号转导、G α (i)信号转导事件、A/1类视紫红质样受体、细胞因子-细胞因子受体相互作用和血小板活化。DPYS的表达也与某些免疫细胞浸润相关,并在SARC细胞系中被发现显著下调。结论:ddpys可作为SARC的潜在预后生物标志物和治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current protein & peptide science
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
73
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.
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