Spatial analyses revealed S100P + TFF1 + tumor cells in spread through air spaces samples correlated with undesirable therapy response in non-small cell lung cancer

作者：Guangyu Fan, Tongji Xie, Mengwei Yang, Lin Li, Le Tang, Xiaohong Han, Yuankai Shi · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-05722-6 · 被引用次数：8 · 研究领域：Chronic Obstructive Pulmonary Disease (COPD) Research、Cancer Cells and Metastasis、Lung Cancer Diagnosis and Treatment

Spread through air spaces (STAS) is a recognized aggressive pattern in lung cancer, serving as a crucial risk factor for postoperative recurrence. However, its phenotype and related spatial structure have remained elusive. To address these limitations, we conducted a comprehensive study based on spatial data, analyzing over 30,000 spots from 14 non-STAS samples and one STAS sample. We observed increased proliferation activities and angiogenesis in STAS, identifying S100P as a potential biomarker for STAS. Furthermore, our investigation into the heterogeneity of STAS tumor cells revealed a subset identified as S100P + TFF1 +, exhibiting a negative impact on patients' survival in public datasets. This subtype exhibited the highest activities in the TGFb and hypoxia, suggesting its potential pro-tumor role within the tumor microenvironment. To assess the role of S100P + TFF1 + tumor cells in therapy response, we included data from two clinical trial cohorts (BPI-7711 for EGFR-TKI therapy and ORIENT-3 for immunotherapy). The presence of S100P + TFF1 + tumor cells correlated with worse responses to both EGFR-TKI therapy and immunotherapy. Notably, TFF1 emerged as a serum marker for predicting EGFR-TKI response. Cell-cell communication analysis revealed that the TGFb signaling pathway was the most activated in S100P + TFF1 + tumor cells, with TGFB2-TGFBR2 identified as the main ligand-receptor pair. This was further validated by multiplex immunofluorescence performed on twenty NSCL...