基底细胞（BC）是支气管祖细胞/干细胞，可以再生受损的气道，而吸烟者可能会发生恶性转化。作为肺癌发生早期阶段的模型，我们着手表征从不吸烟者和没有患癌症的经常吸烟者（对照）以及解剖学上远离癌症的经常吸烟者的正常上皮“区域”的细胞学正常 BC 生长。癌症，包括肺腺癌 (LUAD) 和鳞状细胞癌 (LUSC)（病例）。原发性 BC 是通过远离临床或可见病变/肿瘤部位的支气管内刷进行培养和扩增的。通过 qRT-PCR、RNAseq、流式细胞术、免疫荧光和免疫印迹测试供体亚组的生长、形态和潜在分子特征。(a) BC 群体包括上皮细胞粘附分子 (EpCAM) 阳性和阴性细胞亚群； (b) 吸烟降低了整体 BC 增殖，相应地 EpCAMpos/ITGA6 pos/CD24pos 干细胞分数减少了 2.6 倍； (c) LUSC 供体细胞的畸形 BC 增加了 2.8 倍； (d) 从 LUAD 患者获得的细胞显示增殖和 S 期细胞周期分数增加。这些差异对应于：(i) 不同的 NOTCH1/NOTCH2 转录物表达和潜在下游表达的改变 (ii) E-钙粘蛋白 (CDH1)、肿瘤蛋白 63 (TP63)、分泌球蛋白家族 1a 成员 1 (SCGB1A1) 和 Hairy/与 YRPW 基序 1 (HEY1) 相关的分裂增强子； (iii) LUAD 供体 BC 中 EPCAM 表达减少，NK2 同源框-1 (NKX2-1) mRNA 表达增加。这些和其他研究结果表明，供体年龄、吸烟和肺癌病例对照状态对 BC 表型和分子特征的影响，可能表明早期人类肺癌发病过程中 Notch 信号通路失调。© 2024。作者。

Basal cells (BCs) are bronchial progenitor/stem cells that can regenerate injured airway that, in smokers, may undergo malignant transformation. As a model for early stages of lung carcinogenesis, we set out to characterize cytologically normal BC outgrowths from never-smokers and ever-smokers without cancers (controls), as well as from the normal epithelial "field" of ever-smokers with anatomically remote cancers, including lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) (cases).Primary BCs were cultured and expanded from endobronchial brushings taken remote from the site of clinical or visible lesions/tumors. Donor subgroups were tested for growth, morphology, and underlying molecular features by qRT-PCR, RNAseq, flow cytometry, immunofluorescence, and immunoblot.(a) the BC population includes epithelial cell adhesion molecule (EpCAM) positive and negative cell subsets; (b) smoking reduced overall BC proliferation corresponding with a 2.6-fold reduction in the EpCAMpos/ITGA6 pos/CD24pos stem cell fraction; (c) LUSC donor cells demonstrated up to 2.8-fold increase in dysmorphic BCs; and (d) cells procured from LUAD patients displayed increased proliferation and S-phase cell cycle fractions. These differences corresponded with: (i) disparate NOTCH1/NOTCH2 transcript expression and altered expression of potential downstream (ii) E-cadherin (CDH1), tumor protein-63 (TP63), secretoglobin family 1a member 1 (SCGB1A1), and Hairy/enhancer-of-split related with YRPW motif 1 (HEY1); and (iii) reduced EPCAM and increased NK2 homeobox-1 (NKX2-1) mRNA expression in LUAD donor BCs.These and other findings demonstrate impacts of donor age, smoking, and lung cancer case-control status on BC phenotypic and molecular traits and may suggest Notch signaling pathway deregulation during early human lung cancer pathogenesis.© 2024. The Author(s).