Characterization of lactylation-based phenotypes and molecular biomarkers in sepsis-associated acute respiratory distress syndrome
Abstract 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-as...
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| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-96969-6 |
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| author | Yiheng Wang An Wei Zixuan Su Yunyi Shi Xinqiu Li Lixian He |
| author_facet | Yiheng Wang An Wei Zixuan Su Yunyi Shi Xinqiu Li Lixian He |
| author_sort | Yiheng Wang |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-3f8ea30e5ef045cebd2e28549b2e5e62 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-3f8ea30e5ef045cebd2e28549b2e5e622025-08-20T02:19:58ZengNature PortfolioScientific Reports2045-23222025-04-0115111310.1038/s41598-025-96969-6Characterization of lactylation-based phenotypes and molecular biomarkers in sepsis-associated acute respiratory distress syndromeYiheng Wang0An Wei1Zixuan Su2Yunyi Shi3Xinqiu Li4Lixian He5Department of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Ophthalmology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Ophthalmology, The First Affiliated Hospital, Hengyang Medical School, University of South ChinaAbstract 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.https://doi.org/10.1038/s41598-025-96969-6LactylationSepsis-associated acute respiratory distress syndromeHeterogeneityPhenotypeMolecular biomarkersCirculating immune cells |
| spellingShingle | Yiheng Wang An Wei Zixuan Su Yunyi Shi Xinqiu Li Lixian He Characterization of lactylation-based phenotypes and molecular biomarkers in sepsis-associated acute respiratory distress syndrome Scientific Reports Lactylation Sepsis-associated acute respiratory distress syndrome Heterogeneity Phenotype Molecular biomarkers Circulating immune cells |
| title | Characterization of lactylation-based phenotypes and molecular biomarkers in sepsis-associated acute respiratory distress syndrome |
| title_full | Characterization of lactylation-based phenotypes and molecular biomarkers in sepsis-associated acute respiratory distress syndrome |
| title_fullStr | Characterization of lactylation-based phenotypes and molecular biomarkers in sepsis-associated acute respiratory distress syndrome |
| title_full_unstemmed | Characterization of lactylation-based phenotypes and molecular biomarkers in sepsis-associated acute respiratory distress syndrome |
| title_short | Characterization of lactylation-based phenotypes and molecular biomarkers in sepsis-associated acute respiratory distress syndrome |
| title_sort | characterization of lactylation based phenotypes and molecular biomarkers in sepsis associated acute respiratory distress syndrome |
| topic | Lactylation Sepsis-associated acute respiratory distress syndrome Heterogeneity Phenotype Molecular biomarkers Circulating immune cells |
| url | https://doi.org/10.1038/s41598-025-96969-6 |
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