Contribution of crosstalk of mesothelial and tumoral epithelial cells in pleural metastasis of lung cancer

作者：Peiheng Li, Xin Zhang, Huayun Yan, Xuyang Xia, Yiqi Deng, Qiang Miao, Yiqiao Luo, Guihong Liu, Han Luo, Yan Zhang, Heng Xu, Lili Jiang, Zhihui Li, Yang Shu · 发表于：Translational Lung Cancer Research · 年份：2024 · DOI：10.21037/tlcr-24-118 · 被引用次数：5 · 研究领域：Pleural and Pulmonary Diseases、Cancer Cells and Metastasis、Occupational and environmental lung diseases

Background: Tumor metastasis commonly affects pleura in advanced lung cancer and results in malignant pleural effusion (MPE). MPE is related to poor prognosis, but without systematic investigation on different cell types and their crosstalk at single cell resolution. Methods: We conducted single-cell RNA-sequencing (scRNA-seq) of lung cancer patients with pleural effusion. Next, our data were integrated with 5 datasets derived from individuals under normal, non-malignant disease and lung carcinomatous conditions. Mesothelial cells were re-clustered and their interactions with epithelial cells were comprehensively analyzed. Taking advantage of inferred ligand-receptor pairs, a prediction model of prognosis was constructed. The co-culture of mesothelial cells and malignant epithelial cells in vitro and RNA-seq was performed. Epidermal growth factor receptor (EGFR) antagonist cetuximab was utilized to prevent the lung cancer cells’ invasiveness. Spatial distribution of cells in lung adenocarcinoma patients’ samples were also analyzed to validate our findings. Results: The most distinctive transcriptome profiles between tumor and control were revealed in mesothelial cells, which is the predominate cell type of pleura. Five subtypes were divided, including one predominately identified in MPE which was characterized by enriched cancer-related pathways (e.g., cell migration) along evolutionary trajectory from normal mesothelial cells. Cancer-associated mesothelial cells (CAMCs) exhi...