High-resolution transcriptomics analysis of CXCL13+ EPSTI1+ CDK1+ cells with a specific focus on lung adenocarcinoma

作者：Longjin Zeng, Xu Chen, Jianxiong Cui, Longyao Zhang, Lingchen Li, Chenrui Yin, Xiewan Chen, Jianguo Sun · 发表于：Journal of Thoracic Disease · 年份：2024 · DOI：10.21037/jtd-23-1164 · 被引用次数：12 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Lung Cancer Treatments and Mutations

Background: Programmed cell death ligand 1 (PD-L1) blocking therapy has transformed the treatment of lung adenocarcinoma (LUAD), which has significantly changed the landscape of immunotherapy. We aimed to explore specific cell subpopulations to understand tumor progression and identify markers of response to PD-L1 blocking therapy. Methods: Bulk, fluorescence-activated cell sorting (FACS), and single-cell RNA (scRNA) sequencing were used to profile CXCL13, EPSTI1, and CDK1. The gene set variation analysis (GSVA) R package was utilized for score calculation, and prognostic analyses included receiver operating characteristic (ROC) curves, Cox proportional hazard models, and meta-analysis. Additionally, we analyzed tumor microenvironment (TME), genomics, compound perturbations, and clinical indicators. The high-dimensional analysis captured the intrinsic characteristics of the subpopulation. Furthermore, subpopulation differential genes were used for enrichment analysis of transcription factors and compounds. Results: Literature and website analyses supported the essential role of CXCL13, CDK1, and EPSTI1 in immunotherapy. This led us to focus specifically on LUAD by representing a pan-cancer profile of immune-sensitive genes. Logically, the high-characteristic population may consist of samples positive for CXCL13, EPSTI1, and CDK1. The three-gene signature was a favorable indicator of immunotherapy response in the Stand Up to Cancer-Mark Foundation (SU2C-MARK) LUAD cohort but s...