MicroRNAs Biomarkers and Pathway Enrichment Analysis in Severe Pulmonary Hemorrhagic Syndrome due to Leptospirosis: A Multi-Omics and Multi-Center Study

ABSTRACT: Background. Leptospirosis is among the most widespread zoonoses worldwide. Severe pulmonary hemorrhagic syndrome (SPHS) represents a serious complication of leptospirosis, with poor understanding of its underlying mechanisms and an urgent need for identification of effective biomarkers. Methods. A nested case-control analysis of the blood specimens obtained from two previous multi-center cohorts was conducted. Candidate microRNAs were initially discovered through a global profiling of 800 serum microRNAs, then validated using real-time polymerase-chain reactions. We further conducted a multi-omics analysis incorporating transcriptomic and proteomic data to identify enriched pathways through which the newly identified microRNAs could regulate. Findings. A total of 28 SPHS and 140 non-SPHS patients were evaluated by serum microRNA profiling, revealing distinct expression patterns between the two phenotypes. From the top 81 significantly expressed microRNAs, seven were selected for validation. Among these, miR-5010-3p and miR-147b-3p had area under the curve (AUC) values of 0.72 (95% CI: 0·62–0·81) and 0·66 (95% CI: 0·55–0·76) for discriminating SPHS. Notably, the two microRNAs could detect SPHS in patients who were yet to manifest chest radiograph shadows at the time of sample collection, and in a subgroup of patients who were recruited on day 2 of illness or earlier, with consistent AUC values. Integrated gene-protein pathway enrichment analysis revealed numerous pathways involving host immune responses. Among these, the tumor necrosis factor signaling pathway was the most significant with many of its member genes being targeted by miR-5010-3p or miR-147b-3p.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Leptospira

TISSUE(S): Blood Plasma

DISEASE(S): Severe Acute Respiratory Syndrome

SUBMITTER: PHU TRAN  

LAB HEAD: Phu Nguyen Trong Tran

PROVIDER: PXD052319 | Pride | 2026-02-09

REPOSITORIES: Pride