Single-cell RNA sequencing reveals immune microenvironment niche transitions during the invasive and metastatic processes of ground-glass nodules and part-solid nodules in lung adenocarcinoma by Yi-Feng Ren1,2†, Qiong Ma1†, Xiao Zeng1†, Chun-Xia Huang1, Jia-Li Ren3, Fang Li1, Jia-Jing Tong3, Jia-Wei He1, instant download

Single-cell RNA sequencing reveals immune microenvironment niche transitions during the invasive and metastatic processes of ground-glass nodules and part-solid nodules in lung adenocarcinoma by Yi-Feng Ren1,2†, Qiong Ma1†, Xiao Zeng1†, Chun-Xia Huang1, Jia-Li Ren3, Fang Li1, Jia-Jing Tong3, Jia-Wei He1, instant download

Molecular Cancer,AbstractBackground Radiographically, ground-glass nodules (GGN) and part-solid nodules (PSN) in lung adenocarcinoma (LUAD) have signifcant heterogeneity in their clinical manifestations, biological characteristics, and prognosis. This study aimed to explore the heterogeneity of LUAD in diferent radiological phenotypes and associated factors infuencing tumor evolution.Methods We performed single-cell RNA sequencing (scRNA-seq) on tumor tissues from eight and seven cases of GGN– and PSN–LUAD, respectively, at diferent disease stages, including minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IAC), and metastatic lung cancer (MLC). Additionally, we analyzed adjacent normal tissues from four cases. Immunohistochemistry, multiplex immunofuorescence, and external scRNA-seq data were employed to confrm the expression of signature genes as well as the distribution patterns of CXCL9+TAMs and TREM2+TAMs. A LUAD mouse model was generated using gene editing, organoid culture, and orthotopic transplantation techniques, and comprehensive analyses such as histopathology, RNA sequencing, and Western blotting were performed to validate key pathways.Results Diverse cellular compositions were observed in the tumor microenvironment (TME) during GGN– and PSN–LUAD invasion and metastasis. Notably, CXCL9+and TREM2+tumor-associated macrophages (TAMs) exhibited the most signifcant enrichment changes. It was found that GGN–LUAD exhibited a stronger immune response than PSN–LUAD, with increased interaction between CXCL9+TAMs and CD8+tissue-resident memory T cells during invasion stage (MIA–IAC). Conversely, greater interactions between TREM2+TAMs and tumor cells were observed in PSN–LUAD during the MLC stage. Additionally, TREM2+TAMs were found to diferentiate into TREM2+/SPP1+and