Ren Hanxiao, Du Meng-Ze, Liao Yulin, Zu Ruiling, Rao Lubei, Xiang Run, Zhang Xingmei, Liu Shan, Zhang Peiyin, Leng Ping, Qi Ling, Luo Huaichao
College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People's Republic of China.
Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of the University of Electronic Science and Technology of China, Chengdu, China.
J Cell Mol Med. 2024 Dec;28(24):e70233. doi: 10.1111/jcmm.70233.
This study investigates platelet-related subtypes in non-small cell lung cancer (NSCLC) and seeks to identify genes associated with prognosis, focusing on the clinical significance of the chloride ion channel gene BEST3. We utilised sequencing and clinical data from GEO, TCGA and the Xena platform, building a risk model based on genetic features. TCGA and GSE37745 served as training cohorts, while GSE50081, GSE13213, GSE30129 and GSE42127 were validation cohorts. Immunotherapy datasets (GSE135222, TCGA-SKCM) were also analysed. Differentially expressed genes (DEGs) were identified using Limma, subtypes through ConsensusClusterPlus and key prognostic genes using COX regression, Random Forest and LASSO-COX. BEST3 expression was validated by flow cytometry (FCM) and functional assays in A549 cells with lentiviral overexpression evaluated its impact on apoptosis, proliferation and migration. Three platelet-related subtypes were identified, with ten key prognostic genes (including BEST3). Gene Ontology (GO) analysis showed six genes involved in platelet pathways. BEST3 was highly expressed in the platelet subtype 1. Flow cytometry confirmed elevated BEST3 levels in NSCLC (35.9% vs. 27.3% in healthy individuals). Overexpression of BEST3 in NSCLC cells suppressed apoptosis and promoted proliferation and migration. The discovery of three platelet subtypes and the role of BEST3 in promoting tumour growth and migration highlights its potential as a therapeutic target and prognostic marker in NSCLC.
本研究调查非小细胞肺癌（NSCLC）中与血小板相关的亚型，并试图确定与预后相关的基因，重点关注氯离子通道基因BEST3的临床意义。我们利用来自GEO、TCGA和Xena平台的测序和临床数据，基于基因特征构建了一个风险模型。TCGA和GSE37745作为训练队列，而GSE50081、GSE13213、GSE30129和GSE42127作为验证队列。还分析了免疫治疗数据集（GSE135222、TCGA-SKCM）。使用Limma鉴定差异表达基因（DEG），通过ConsensusClusterPlus鉴定亚型，使用COX回归、随机森林和LASSO-COX鉴定关键预后基因。通过流式细胞术（FCM）验证BEST3表达，并在A549细胞中进行功能测定，用慢病毒过表达评估其对细胞凋亡、增殖和迁移的影响。确定了三种与血小板相关的亚型，有十个关键预后基因（包括BEST3）。基因本体论（GO）分析显示有六个基因参与血小板途径。BEST3在血小板亚型1中高表达。流式细胞术证实NSCLC中BEST3水平升高（健康个体中为27.3%，NSCLC中为35.9%）。NSCLC细胞中BEST3的过表达抑制细胞凋亡并促进增殖和迁移。三种血小板亚型的发现以及BEST3在促进肿瘤生长和迁移中的作用突出了其作为NSCLC治疗靶点和预后标志物的潜力。
