Spatial transcriptomic analysis across histological subtypes reveals molecular heterogeneity and prognostic markers in early‐stage lung adenocarcinoma

作者：Hua Geng, Wenhao Zhou, Haitao Luo, Jiaqian Wang, Shixiong Li, Congcong Song, Yujie Zhao, Meilin Xu · 发表于：Clinical and Translational Medicine · 年份：2025 · DOI：10.1002/ctm2.70439 · 被引用次数：5 · 研究领域：Ferroptosis and cancer prognosis、Single-cell and spatial transcriptomics、Lung Cancer Diagnosis and Treatment

BACKGROUND: The progression and prognosis of early-stage lung adenocarcinoma are closely associated with histologic subtypes, yet the presence of mixed histologic patterns often complicates prognostic assessment. Currently, the correlation between molecular and histologic features remains poorly understood. METHODS: Formalin-fixed paraffin-embedded (FFPE) samples were collected from patients with primary early-stage lung adenocarcinoma, encompassing three histologic subtypes: well-differentiated, moderately differentiated, and poorly differentiated. The GeoMx Digital Spatial Profiler platform was utilized to obtain spatial transcriptomic profiling. Regions of interest were carefully selected and further subdivided into three categories of areas of interest, specifically epithelial cell-enriched regions, macrophage-enriched regions, and other regions. Multiplex immunofluorescence (mIF) assays were employed to validate the obtained results. RESULTS: Distinct molecular characteristics were identified in tumor epithelial- and macrophage-enriched compartments spanning well-differentiated to poorly differentiated tumors. In poorly differentiated tumors, we observed enrichment of pathways related to humoral immune response, complement activation regulation, and extracellular matrix receptor interaction pathways, all of which are significantly associated with poorer prognosis. We integrated these pathways to develop a composite molecular signature that strongly correlate with adverse...