Shi Jianguang, Wang Zishan, Guo Jing, Chen Yingqi, Tong Changyong, Tong Jingjie, Hu Wentao, Li Chenwei, Li Xinjian
Thoracic Surgery Department, Ningbo First Hospital, Ningbo, China.
Front Oncol. 2021 Oct 21;11:726834. doi: 10.3389/fonc.2021.726834. eCollection 2021.
Epithelial-mesenchymal transition (EMT) process, which is regulated by genes of inducible factors and transcription factor family of signaling pathways, transforms epithelial cells into mesenchymal cells and is involved in tumor invasion and progression and increases tumor tolerance to clinical interventions. This study constructed a multigene marker for lung predicting the prognosis of lung adenocarcinoma (LUAD) patients by bioinformatic analysis based on EMT-related genes. Gene sets associated with EMT were downloaded from the EMT-gene database, and RNA-seq of LUAD and clinical information of patients were downloaded from the TCGA database. Differentially expressed genes were screened by difference analysis. Survival analysis was performed to identify genes associated with LUAD prognosis, and overlapping genes were taken for all the three. Prognosis-related genes were further determined by combining LASSO regression analysis for establishing a prediction signature, and the risk score equation for the prognostic model was established using multifactorial COX regression analysis to construct a survival prognostic model. The model accuracy was evaluated using subject working characteristic curves. According to the median value of risk score, samples were divided into a high-risk group and low-risk group to observe the correlation with the clinicopathological characteristics of patients. Combined with the results of one-way COX regression analysis, HGF, PTX3, and S100P were considered as independent predictors of LUAD prognosis. In lung cancer tissues, HGF and PTX3 expression was downregulated and S100P expression was upregulated. Kaplan-Meier, COX regression analysis showed that HGF, PTX3, and S100P were prognostic independent predictors of LUAD, and high expressions of all the three were all significantly associated with immune cell infiltration. The present study provided potential prognostic predictive biological markers for LUAD patients, and confirmed EMT as a key mechanism in LUAD progression.
上皮-间质转化（EMT）过程由诱导因子基因和信号通路的转录因子家族调控，可将上皮细胞转化为间充质细胞，参与肿瘤侵袭和进展，并增加肿瘤对临床干预的耐受性。本研究通过基于EMT相关基因的生物信息学分析，构建了一个用于预测肺腺癌（LUAD）患者预后的多基因标志物。从EMT基因数据库下载与EMT相关的基因集，并从TCGA数据库下载LUAD的RNA测序数据和患者的临床信息。通过差异分析筛选差异表达基因。进行生存分析以鉴定与LUAD预后相关的基因，并取三者的重叠基因。通过结合LASSO回归分析进一步确定预后相关基因以建立预测特征，并使用多因素COX回归分析建立预后模型的风险评分方程以构建生存预后模型。使用受试者工作特征曲线评估模型准确性。根据风险评分的中位数，将样本分为高风险组和低风险组，以观察与患者临床病理特征的相关性。结合单向COX回归分析结果，将HGF、PTX3和S100P视为LUAD预后的独立预测因子。在肺癌组织中，HGF和PTX3表达下调，S100P表达上调。Kaplan-Meier、COX回归分析表明，HGF、PTX3和S100P是LUAD预后的独立预测因子，三者的高表达均与免疫细胞浸润显著相关。本研究为LUAD患者提供了潜在的预后预测生物学标志物，并证实EMT是LUAD进展的关键机制。
