A single-cell characterised signature integrating heterogeneity and microenvironment of lung adenocarcinoma for prognostic stratification

作者：Jiachen Xu, Yundi Zhang, Man Li, Zhuo Shao, Yiting Dong, Qingqing Li, Hua Bai, Jianchun Duan, Jia Zhong, Rui Wan, Jing Bai, Xin Yi, Fuchou Tang, Jie Wang, Zhijie Wang · 发表于：EBioMedicine · 年份：2024 · DOI：10.1016/j.ebiom.2024.105092 · 被引用次数：25 · 研究领域：Ferroptosis and cancer prognosis、Cancer Immunotherapy and Biomarkers、Single-cell and spatial transcriptomics

BACKGROUND: The high heterogeneity of tumour and the complexity of tumour microenvironment (TME) greatly impacted the tumour development and the prognosis of cancer in the era of immunotherapy. In this study, we aimed to portray the single cell-characterised landscape of lung adenocarcinoma (LUAD), and develop an integrated signature incorporating both tumour heterogeneity and TME for prognosis stratification. METHODS: Single-cell tagged reverse transcription sequencing (STRT-seq) was performed on tumour tissues and matched normal tissues from 14 patients with LUAD for immune landscape depiction and candidate key genes selection for signature construction. Kaplan-Meier survival analyses and in-vitro cell experiments were conducted to confirm the gene functions. The transcriptomic profile of 1949 patients from 11 independent cohorts including nine public datasets and two in-house cohorts were obtained for validation. FINDINGS: We selected 11 key genes closely related to cell-to-cell interaction, tumour development, T cell phenotype transformation, and Ma/Mo cell distribution, including HLA-DPB1, FAM83A, ITGB4, OAS1, FHL2, S100P, FSCN1, SFTPD, SPP1, DBH-AS1, CST3, and established an integrated 11-gene signature, stratifying patients to High-Score or Low-Score group for better or worse prognosis. Moreover, the prognostically-predictive potency of the signature was validated by 11 independent cohorts, and the immunotherapeutic predictive potency was also validated by our in-house...