Abstract
Aortic dissection (AD) is a life-threatening aortic disease with limited disease-modifying pharmacologic options. Lysine lactylation is a metabolism-linked post-translational modification implicated in vascular and inflammatory biology, but its relationship to AD has not been well characterized. Public AD transcriptomic datasets were integrated for differential expression analysis and WGCNA. Lactylation-related DEGs were defined by intersecting DEGs with a curated lactylation-related gene set. Candidate genes were prioritized using complementary machine-learning models (LASSO, Random Forest, and XGBoost) as a feature-screening strategy with internal resampling and hold-out validation (cross-validation and a hold-out set). GFM1 expression was assessed by qRT-PCR and western blotting in human aortic tissues. Functional relevance was examined in primary mouse aortic vascular smooth muscle cells (VSMCs) using siRNA knockdown under angiotensin II stimulation (1.0 µmol/L, 24 h), with proliferation and migration assessed by CCK-8, EdU, Transwell, and scratch-wound assays. We identified 217 DEGs and an AD-associated co-expression module. Intersection analysis yielded 11 lactylation-related DEGs, among which GFM1 received consistent support across models. GFM1 showed higher expression in AD tissues, and GFM1 knockdown attenuated angiotensin II–induced VSMCs proliferation and migration. Integrated transcriptomics and machine-learning–based prioritization nominate GFM1 as a lactylation-related candidate associated with AD, warranting further investigation. These findings are hypothesis-generating: model performance reflects internal evaluation only, and independent external validation and direct lactylation profiling are required to establish generalizability and clarify mechanistic links.
Data availability
The integrated transcriptomic data are available from GEO (GSE52093, GSE98770, GSE153434, GSE147026). Full uncropped gels and blots have been provided as Supplementary File 1. De-identified raw data underlying qPCR/WB and cell-based assays are available from the corresponding author upon reasonable request under an institutional agreement.
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Acknowledgements
We appreciate the surgeons and nurses from the Department of Cardiovascular Surgery for their advice and helpful information. Thanks to the faculty of the Institute of Cardiovascular Disease.
Funding
This work was supported by the Tianjin Key Medical Discipline (Specialty) Construction Project (No. TJYXZDXK-3–030C) and the Tianjin Education Commission Research Program Project (No. 2022YGYB09), and the Tianjin Municipal Science and Technology Program (No. 20JCZDJC00810).
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J.C. conceived the study, designed the analyses, performed data integration and WGCNA/ML modeling, prepared the figures, and drafted the manuscript. N.J. processed samples and performed qRT-PCR validation, curated clinical/experimental data, revised figures, and contributed to manuscript editing. Z.G. and Y.B. are co-corresponding authors. Z.G. provided clinical resources and supervision, oversaw project administration, and critically revised the manuscript. Y.B. provided senior supervision, secured funding, and critically reviewed and improved the manuscript; Y.B. serves as guarantor of the work. All authors read and approved the final manuscript and agree to be accountable for all aspects of the work.
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Clinical trial number: not applicable. The studies involving human participants were reviewed and approved by the Ethics Committee of Tianjin Chest Hospital (approval No. 2023LW-001). The patients/participants provided their written informed consent to participate in this study. All methods were performed in accordance with the relevant guidelines and regulations and with the Declaration of Helsinki. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. No live animals were used in this study. Primary mouse aortic VSMCs were commercially obtained. According to the vendor’s documentation, these primary cells were procured under protocols approved by the vendor’s Institutional Animal Care and Use Committee (IACUC) and in accordance with relevant guidelines. Because the study involved only commercially sourced primary cells and no procedures on live animals at our institution, institutional animal ethics approval was not required.
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Chen, J., Jiang, N., Guo, Z. et al. Machine-learning–guided transcriptomic integration identifies GFM1 as a lactylation-related candidate biomarker in aortic dissection. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40139-9
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DOI: https://doi.org/10.1038/s41598-026-40139-9
