Characterizing the Association between GOLM1 and MASH-related Fibrosis through Multi-cohort Transcriptomic Analysis and AI-assisted Validation

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Hepatic fibrosis is the principal determinant of long-term prognosis in metabolic dysfunction-associated steatohepatitis (MASH), yet hepatocyte-derived secreted mediators that directly drive fibrotic progression remain insufficiently characterized. In this study, differential expression analysis and cross-cohort Venn diagram intersection were performed across three independent GEO datasets, identifying five candidate genes consistently and significantly upregulated across both MASH and fibrosis progression. Among these, GOLM1 was selected as the primary candidate, as it is the only gene with functional evidence supporting proteolytic cleavage-mediated secretion and potential paracrine signaling to adjacent fibroblasts. GOLM1 expression was consistently and significantly elevated across all three cohorts and showed a stage-dependent progressive increase with advancing fibrosis stage. For unbiased genome-wide validation, AI-based Random Forest analysis was performed on the complete GSE49541 expression matrix comprising 54,675 probes, ranking GOLM1 in the top 0.8% (rank 462/54,675); single-gene logistic regression with 5-fold stratified cross-validation achieved an AUC of 0.77 ± 0.11. Spatial transcriptomic analysis of two independent datasets using the SpatialDB Liver Zonation database consistently revealed periportal-enriched expression of GOLM1, with the highest expression in Zone 1 (periportal zone) and a progressive decrease toward Zone 3 (pericentral zone) in both datasets. Together, these findings suggest that GOLM1 overexpressed in periportal hepatocytes may be secreted and act in a paracrine manner on adjacent portal fibroblasts to promote MASH-associated fibrosis, positioning GOLM1 as a novel candidate mechanistic mediator and biomarker target in MASH-related fibrosis.

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