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This study aimed to dissect the stromal landscape of LUAD with bone metastases. Unsupervised clustering of scRNA\u2010seq data from LUAD patients with bone metastasis identifies stromal subsets. Pseudotime analysis combined with CytoTRACE stemness scoring reconstructs mesenchymal stromal cell (MSC) differentiation trajectories, while CellChat characterizes cell\u2013cell communication networks among MSC subpopulations. Differentially expressed genes (DEGs) specific to functionally distinct MSC subsets are subjected to LASSO\u2010Cox regression for construction of a prognostic RiskScore model, which is validated in independent bulk RNA\u2010seq cohorts regarding overall survival, immune cell infiltration, and drug sensitivity. A distinct high\u2010stemness MSC C1 subpopulation is localized at the bifurcation point of two divergent differentiation trajectories toward a matrix\u2010remodeling fate and a secretory, immunomodulatory phenotype. The RiskScore model stratifies patients into low\u2010 and high\u2010risk groups with divergent overall\u2010survival outcomes. Reduced infiltration of cytotoxic lymphocytes is observed in high\u2010risk patients, and higher drug sensitivity within the high\u2010risk subgroup. In\u00a0vitro assays verify that LDHA knockdown impairs proliferation and migration in A549 cells. This study provides a rationale for targeting stroma\u2010derived genes in risk\u2010adapted therapy.<\/jats:p>","DOI":"10.1111\/cbdd.70414","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:21:42Z","timestamp":1792470102000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MSC C1<\/scp>\n                    : A Potential Hub Linking Stromal Plasticity, Immune Regulation, and Patient Survival in Lung Adenocarcinoma"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9134-7244","authenticated-orcid":false,"given":"Houlei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopedics Shanghai Geriatric Medical Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianle","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Geriatric 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