MSC C1 : A Potential Hub Linking Stromal Plasticity, Immune Regulation, and Patient Survival in Lung Adenocarcinoma
Year: 2026
Type: article
Abstract: Bone metastasis of lung adenocarcinoma (LUAD) directly leads to poor prognosis. This study aimed to dissect the stromal landscape of LUAD with bone metastases. Unsupervised clustering of scRNA-seq 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-cell communication networks among MSC subpopulations. Differentially expressed genes (DEGs) specific to functionally distinct MSC subsets are subjected to LASSO-Cox regression for construction of a prognostic RiskScore model, which is validated in independent bulk RNA-seq cohorts regarding overall survival, immune cell infiltration, and drug sensitivity. A distinct high-stemness MSC C1 subpopulation is localized at the bifurcation point of two divergent differentiation trajectories toward a matrix-remodeling fate and a secretory, immunomodulatory phenotype. The RiskScore model stratifies patients into low- and high-risk groups with divergent overall-survival outcomes. Reduced infiltration of cytotoxic lymphocytes is observed in high-risk patients, and higher drug sensitivity within the high-risk subgroup. In vitro assays verify that LDHA knockdown impairs proliferation and migration in A549 cells. This study provides a rationale for targeting stroma-derived genes in risk-adapted therapy.
Source: Chemical Biology & Drug Design
DOI: 10.1111/cbdd.70414
Authors: Houlei Wang, Tianle Ma, Chao Jia, Chunhui Ma
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,920
OpenAlex ID: W7223037717