Single‐cell RNA sequencing reveals the multi‐cellular ecosystem in different radiological components of pulmonary part‐solid nodules

血管生成 克拉斯 病理 细胞 癌症研究 实体瘤 生物 化学 医学 癌症 结直肠癌 生物化学 遗传学
作者
Yanmeng Li,Xiao Li,Haiming Chen,Kunkun Sun,Hao Li,Ying Zhou,Jun Wang,Fan Bai,Fan Yang
出处
期刊:Clinical and translational medicine [Wiley]
卷期号:12 (2) 被引量:13
标识
DOI:10.1002/ctm2.723
摘要

Abstract Background Early‐stage lung adenocarcinoma that radiologically manifests as part‐solid nodules, consisting of both ground‐glass and solid components, has distinctive growth patterns and prognosis. The characteristics of the tumour microenvironment and transcriptional features of the malignant cells of different radiological phenotypes remain poorly understood. Methods Twelve treatment‐naive patients with radiological part‐solid nodules were enrolled. After frozen pathology was confirmed as lung adenocarcinoma, two regions (ground‐glass and solid) from each of the 12 part‐solid nodules and 5 normal lung tissues from 5 of the12 patients were subjected to single‐cell sequencing by 10 x Genomics. We used Seurat v3.1.5 for data integration and analysis. Results We comprehensively dissected the multicellular ecosystem of the ground‐glass and solid components of part‐solid nodules at the single‐cell resolution. In tumours, these components had comparable proportions of malignant cells. However, the angiogenesis, epithelial‐to‐mesenchymal transition, KRAS, p53, and cell‐cycle signalling pathways were significantly up‐regulated in malignant cells within solid components compared to those within ground‐glass components. For the tumour microenvironment, the relative abundance of myeloid and NK cells tended to be higher in solid components than in ground‐glass components. Slight subtype composition differences existed between the ground‐glass and solid components. The T/NK cell subsets’ cytotoxic function and the macrophages’ pro‐inflammation function were suppressed in solid components. Moreover, pericytes in solid components had a stronger communication related to angiogenesis promotion with endothelial cells and tumour cells. Conclusion The cellular landscape of ground‐glass components is significantly different from that of normal tissue and similar to that of solid components. However, transcriptional differences exist in the vital signalling pathways of malignant and immune cells within these components.
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