{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:04:34Z","timestamp":1785179074309,"version":"3.55.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Dysregulated immune response in trauma and sepsis leads to the abnormal activation of the complement and coagulation systems. Mannose-binding lectin (MBL)-associated serine protease-1 (MASP-1) activates the lectin pathway of the complement system and mediates proinflammatory and procoagulant reactions. However, the potential effects of MASP-1 in trauma and sepsis have not yet been explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We obtained five sepsis, two trauma, and one sepsis and trauma RNA-sequencing dataset from the Gene Expression Omnibus (GEO) database and conducted a comprehensive evaluation of the expression pattern, biological functions, and diagnostic value of MASP-1 in trauma and sepsis. Additionally, we investigated the association between MASP-1 expression and clinicopathological characteristics of trauma and sepsis. Furthermore, we collected clinical specimens to preliminarily validate the expression level and diagnostic efficacy of MASP-1 as well as the correlation of MASP-1 with clinical features of trauma and sepsis. Subsequently, we conducted a correlation analysis among MASP-1, immune cell infiltration, and immune and molecular pathways. Finally, we mechanistically analyzed the relationship among MASP-1, specific immune cells, and pivotal molecular pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>MASP-1<\/jats:italic> expression was significantly upregulated in the trauma\/sepsis samples compared to the control samples in the GEO datasets. MASP-1 exhibited excellent diagnostic values (AUC\u2009&amp;gt;\u20090.7) in multiple datasets and at multiple time points and could efficiently distinguish trauma\/sepsis samples from the control samples. Moreover, <jats:italic>MASP-1<\/jats:italic> expression was significantly positively correlated with the severity of the disease (APACHE-II, CRP, and neutrophil levels). These results were further validated by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Functional enrichment analysis revealed that MASP-1 primarily promotes trauma and sepsis via the immune-related signaling pathway. MASP-1 was significantly correlated with the infiltration of specific immune cells (such as B cells, CD8 T cells, neutrophils, macrophages, and infiltrating lymphocytes) and immune and molecular pathways (such as checkpoint, HLA, IL6\/JAK\/STAT3 signaling, necrosis, T-cell co-inhibition, and T-cell co-stimulation). Finally, analysis of the transcription and single-cell data revealed that MASP-1 was specifically expressed in T cells, and further correlation analysis revealed a close correlation between MASP-1 expression, proportion of CD8 T cells, and IL6\/JAK\/STAT3 signaling scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that MASP-1 can serve as an immune-related biomarker for the diagnosis and disease severity of trauma and sepsis. It may activate the IL6 JAK-STAT3 signaling pathway and promote CD8 T-cell depletion to trigger traumatic sepsis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2024.1320811","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T04:22:41Z","timestamp":1707279761000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Systematic analysis of MASP-1 serves as a novel immune-related biomarker in sepsis and trauma followed by preliminary experimental validation"],"prefix":"10.3389","volume":"11","author":[{"given":"Lina","family":"Xian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaowen","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhui","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1097\/TA.0000000000004081","article-title":"Damage-control resuscitation in pediatric trauma: what you need to know","volume":"95","author":"Russell","year":"2023","journal-title":"J. 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