The Potential Role of C4 MYH11+ Fibroblasts and the MDK-SDC2 Ligand-Receptor Pair in Lung Adenocarcinoma: Implications for Prognosis and Therapeutic Strategies.

BACKGROUNDLung adenocarcinoma (LUAD) posed a significant threat to global human health. This study employed single-cell RNA sequencing (scRNA-seq) to analyze transcriptomic data from nine LUAD patients at different stages of tumor infiltration, aiming to elucidate the tumor microenvironment and key biological processes of LUAD.

METHODSIn this study, we processed the scRNA-seq data using the Seurat package and sequentially applied principal component analysis followed by the Harmony package to effectively correct for batch effects, identifying 105,725 high-quality cells. Through cell clustering and gene expression profiling, we identified critical cell subpopulations and gene expression patterns in LUAD patients.

RESULTSOur analysis revealed that the C4 MYH11+ Fibroblasts subtype was primarily involved in biological processes related to muscle function. Further investigations uncovered the MDK-SDC2 ligand-receptor pair as a critical regulator of tumor cell invasion, proliferation, and migration, driving LUAD progression. Additionally, we developed a gene-based prognostic model that effectively predicted patient survival, providing valuable clinical insights.

CONCLUSIONThis study provided a comprehensive atlas of the LUAD tumor microenvironment, highlighted the role of the C4 MYH11+ Fibroblasts in tumor progression. It also proposed the MDK-SDC2 ligand-receptor pair as a novel mechanism, addressing a significant gap in this area of research. And presented a gene-based prognostic model as a novel perspective for research into immunotherapy and drug sensitivity in LUAD.