DPYS作为慢性阻塞性肺疾病严重程度潜在 生物标志物的鉴定与验证
Identification and Validation of DPYS as a Potential Biomarker for the Severity of Disease in Patients with COPD
DOI: 10.12677/acm.2026.1651998, PDF,   
作者: 周新悦, 费广鹤*：安徽医科大学第一附属医院呼吸与危重症医学科，安徽 合肥
关键词: 慢性阻塞性肺疾病；生物标志物；代谢失调；二氢嘧啶酶；Chronic Obstructive Pulmonary Disease； Biomarker； Metabolic Disorder； DPYS
摘要: 目的：慢性阻塞性肺疾病(COPD)的特征是慢性气道炎症和进行性气流受限，并伴有全身代谢失调，然而用于评估疾病严重程度的代谢相关生物标志物仍有待探索。本研究旨在通过生物信息学分析鉴定与COPD严重程度代谢相关基因，并在临床样本中进行验证。方法：从GEO数据库中的GSE76925中获取基因表达谱，从MSigDB数据库获取代谢相关基因。采用最小绝对收缩和选择算子(LASSO)回归、功能富集和相关性分析来筛选核心基因，通过GSE47460进行外部数据集验证并在临床样本中对关键核心基因进行验证。结果：从GSE76925中鉴定出339个COPD相关的差异表达基因(DEGs)，在GSEA网站的KEGG代谢通路中获取948个与代谢相关的基因，交集后获得19个重叠基因。进一步通过LASSO分析确定了8个关键的COPD代谢相关差异表达基因：TYRP1、HPGDS、SPTLC1、NUDT12、UAP1、CA3、DPYS和PLA2G7。其中，DPYS的表达与FEV1% predicted、FEV1/FVC、%LAA950、Perc15和BMI显著相关(P < 0.05)。在临床样本的验证中，DPYS在COPD患者的肺组织和血清样本中的表达均显著高于对照组，进一步分析发现在Gold 3~4级患者中，其血清DPYS浓度显著高于Gold 1~2级(P < 0.05)。同时血清中DPYS水平与%LAA950呈显著正相关(P < 0.0001)，与FEV1/FVC和FEV1% predicted呈显著负相关(P < 0.05)。在排除了年龄、性别和BMI混杂因素的影响后，多因素Logistic回归分析显示，血清DPYS水平与COPD严重程度(GOLD 1~2级vs 3~4级)显著相关。结论：DPYS可能作为评估COPD严重程度的潜在代谢生物标志物。
Abstract: Objective: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and progressive airflow limitation, often accompanied by systemic metabolic dysregulation. However, metabolic biomarkers for assessing COPD severity remain to be explored. This study aimed to identify metabolism-related genes associated with COPD severity by bioinformatic analysis and to validate it in clinical settings. Methods: Gene expression profiles were obtained from GSE76925 dataset in the GEO database and metabolism-related genes were retrieved from the MSigDB database. The least absolute shrinkage and selection operator (LASSO) regression, the functional enrichment and correlation analyses were used to identify core genes. External validation was conducted using the GSE47460 dataset. The key candidate gene was further validated in the lung tissue and serum samples. Results: A total of 339 COPD differentially expressed genes (DEGs) were identified from GSE76925, and 948 metabolism-related genes were identified from KEGG metabolic pathways in GSEA website. 19 COPD metabolism-related DEGs were co-identified. LASSO regression identified eight key metabolism-related DEGs: TYRP1, HPGDS, SPTLC1, NUDT12, UAP1, CA3, DPYS, and PLA2G7. Notably, the expression of DPYS was significantly correlated with FEV1% predicted, FEV1/FVC, %LAA950, Perc15, and BMI (P < 0.05). Clinical validation demonstrated that DPYS levels in both lung tissue and serum were significantly elevated in COPD patients. Moreover, serum DPYS levels were significantly higher in patients with Gold 3~4 compared to GOLD 1~2 (P < 0.05). Serum DPYS levels were positively correlated with %LAA950 (P < 0.0001) and negatively correlated with FEV1/FVC and FEV1% predicted (P < 0.05). After adjusting for age, sex and BMI, multivariate logistic regression analysis demonstrated that serum DPYS levels were significantly associated with COPD severity. Conclusion: DPYS may serve as a potential metabolism-related biomarker for assessing the severity of COPD.
文章引用：周新悦, 费广鹤. DPYS作为慢性阻塞性肺疾病严重程度潜在 生物标志物的鉴定与验证[J]. 临床医学进展, 2026, 16(5): 1921-1933. https://doi.org/10.12677/acm.2026.1651998

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