Data Sheet 1_Integrative multi-omics analysis prioritizes ALDH2 as a candidate Puerarin-associated target linked to macrophage infiltration in lung adenocarcinoma.doc

Five feature genes (ABCG2, ALDH2, MIF, PTGS1, and SELP) were retained by three machine-learning approaches and ABCG2, ALDH2, MIF, and SELP showed consistent diagnostic performance in the training and validation cohorts. Docking and molecular dynamics simulations predicted favorable and stable modeled interactions of puerarin with ABCG2 and ALDH2, but did not establish direct target engagement. MR using a LUAD outcome dataset suggested an inverse association between genetically predicted ALDH2 expression and LUAD risk.

Single-cell analysis indicated relative enrichment of ALDH2 transcripts in macrophages. In vivo, puerarin reduced orthotopic tumor burden and was accompanied by increased total ALDH2 expression and higher proportions of F4/80⁺CD11b⁺ cells in peripheral blood and tumor tissue.</p>Conclusion<p>Puerarin suppressed tumor growth in a murine LUAD model and was associated with ALDH2 upregulation and increased macrophage infiltration.

Integrated analyses prioritize ALDH2 as a candidate molecule potentially linking puerarin treatment to changes in the tumor immune microenvironment. Direct puerarin–ALDH2 binding, macrophage-specific ALDH2 regulation, and the functional consequences for macrophage polarization require further experimental validation.</p>