Wang Yiheng, Wei An, Su Zixuan, Shi Yunyi, Li Xinqiu, He Lixian
Department of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, 69 Chuanshan Road, Shigu District, Hengyang, 421001, Hunan Province, China.
Department of Ophthalmology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan Province, China.
Sci Rep. 2025 Apr 22;15(1):13831. doi: 10.1038/s41598-025-96969-6.
Sepsis-associated acute respiratory distress syndrome (ARDS) is a heterogeneous disease with high morbidity and mortality. Lactylation plays a crucial role in sepsis and sepsis-induced lung injury. This study aimed to identify distinct lactylation-based phenotypes in patients with sepsis-associated ARDS and determine relevant molecular biomarkers. We analyzed blood transcriptome and clinical data from patients with sepsis-associated ARDS and calculated the lactylation activity. KEGG pathway analysis, drug sensitivity prediction, and immune cell infiltration analysis were performed. Candidate molecular biomarkers were identified by intersecting the feature genes extracted from four machine learning models. Lactylation activity showed significant heterogeneity among patients with sepsis-associated ARDS, which enabled the classification into low- and high-lactylation activity phenotypes. Patients with high-lactylation experienced longer hospital stays and higher mortality rates, as well as distinct signaling pathways, drug responses, and circulating immune cell abundances. Six key markers (ALDOB, CCT5, EP300, PFKP, PPIA, and SIRT1) were identified to differentiate the two lactylation activity phenotypes, all significantly correlated with circulating immune cell populations. This study revealed significant heterogeneity in lactylation activity phenotypes among patients with sepsis-associated ARDS and identified potential biomarkers to facilitate the application of these phenotypes in clinical practice.
脓毒症相关急性呼吸窘迫综合征（ARDS）是一种发病率和死亡率均较高的异质性疾病。乳酰化在脓毒症及脓毒症诱导的肺损伤中起关键作用。本研究旨在识别脓毒症相关ARDS患者中基于乳酰化的不同表型，并确定相关分子生物标志物。我们分析了脓毒症相关ARDS患者的血液转录组和临床数据，并计算了乳酰化活性。进行了KEGG通路分析、药物敏感性预测和免疫细胞浸润分析。通过交叉从四个机器学习模型中提取的特征基因来识别候选分子生物标志物。脓毒症相关ARDS患者的乳酰化活性存在显著异质性，这使得能够将其分为低乳酰化活性表型和高乳酰化活性表型。高乳酰化患者住院时间更长、死亡率更高，且具有不同的信号通路、药物反应和循环免疫细胞丰度。确定了六个关键标志物（醛缩酶B、CCT5、EP300、磷酸果糖激酶P、肽基脯氨酰异构酶A和沉默信息调节因子1）以区分两种乳酰化活性表型，所有这些标志物均与循环免疫细胞群体显著相关。本研究揭示了脓毒症相关ARDS患者乳酰化活性表型存在显著异质性，并确定了潜在生物标志物，以促进这些表型在临床实践中的应用。
