摘要
目的:筛选与肺腺癌(lung adenocarcinoma,LUAD)转移和生存预后密切相关的循环肿瘤细胞(circulating tumor cells,CTCs)差异表达基因,构建基于CTCs的LCD风险评分模型,并评估其在LUAD患者预后中的临床应用价值。方法:从GSE249262数据库获取LUAD患者的CTCs基因表达数据,从TCGA数据库获取439例LUAD患者的肿瘤组织RNA测序数据。通过LASSO回归和Cox比例风险回归分析,筛选出与LUAD预后显著相关的CTCs关键基因。基于这些基因构建LCD风险评分模型,并在3个独立验证集(GSE31210、GSE8894和GSE26939)及南京医科大学附属肿瘤医院的67例LUAD患者队列中进行验证,使用Kaplan-Meier生存分析和受试者工作特征(ROC)曲线评估模型的预测效能。结果:共筛选出6个与LUAD预后密切相关的CTCs关键基因,即TXN、PLP2、H2AFZ、LPGAT1、TFG和BZW1。构建的LCD风险评分模型在训练集和验证集中预测1年、3年和5年生存率的ROC曲线下面积(AUC)均超过0.60。Kaplan-Meier分析显示高风险组总生存期(OS)显著低于低风险组(HR=2.48,P<0.01)。功能富集分析表明,CTCs差异基因主要参与细胞周期调控、染色体分离和免疫逃逸等过程。进一步分析显示,PLP2和LPGAT1的高表达与不良预后显著相关(PLP2:HR=2.0,P=0.0013;LPGAT1:HR=1.8,P=0.0039)。结论:本研究成功构建并验证了一个基于CTCs关键基因的LCD风险评分模型,可为个性化治疗和精准预后评估提供潜在的临床应用价值。
Objective:To identify differentially expressed genes(DEGs)in circulating tumor cells(CTCs)that were closely associated with metastasis and prognosis in lung adenocarcinoma(LUAD)and to construct an LCD risk score model based on CTCs.This model was then evaluated for its clinical utility in prognostic assessment among LUAD patients.Methods:CTCs gene expression data for LUAD patients were obtained from the GSE249262 database,and RNA sequencing data from 439 LUAD tumor samples were obtained from the TCGA database.LASSO regression and Cox proportional hazards regression analyses were conducted to identify CTCs-related key genes significantly associated with LUAD prognosis.An LCD risk score model was established based on these genes and subsequently validated across three independent cohorts(GSE31210,GSE8894,and GSE26939),as well as a clinical cohort comprising 67 LUAD patients from the Affiliated Cancer Hospital of Nanjing Medical University.Kaplan-Meier survival analysis and ROC curves were utilized to evaluate the model s predictive performance.Results:Six key CTCs genes associated with LUAD prognosis were identified:TXN,PLP2,H2AFZ,LPGAT1,TFG,and BZW1.The constructed LCD risk score model achieved AUC values exceeding 0.60 for predicting 1-year,3-year,and 5-year survival rates in both the training and validation cohorts.Kaplan-Meier analysis indicated that the overall survival(OS)in the high-risk group was significantly lower than that in the low-risk group(HR=2.48,P<0.01).Functional enrichment analysis revealed that CTCs-related DEGs were primarily involved in cell cycle regulation,chromosomal segregation,and immune evasion.Further analysis revealed that high expression levels of PLP2 and LPGAT1 were significantly associated with poor prognosis(PLP2:HR=2.0,P=0.0013;LPGAT1:HR=1.8,P=0.0039).Conclusion:This study has successfully developed and validated an LCD risk score model based on key CTCs genes,which holds potential clinical value for personalized treatment and precise prognostic assessment in LUAD patients.
作者
黄兴
冯一鹏
陈辰
李少邱
丁翰林
马大伟
HUANG Xing;FENG Yipeng;CHEN Chen;LI Shaoqiu;DING Hanlin;MA Dawei(Department of Pathology,Affiliated Cancer Hospital of Nanjing Medical University/Jiangsu Cancer Hospital/Jiangsu Institute of Cancer Prevention and Treatment,Nanjing 210009,China;Department of Thoracic Surgery,Affiliated Cancer Hospital of Nanjing Medical University/Jiangsu Cancer Hospital/Jiangsu Institute of Cancer Prevention and Treatment,Nanjing 210009,China;Department of Oncology,Affiliated Cancer Hospital of Nanjing Medical University/Jiangsu Cancer Hospital/Jiangsu Institute of Cancer Prevention and Treatment,Nanjing 210009,China)
出处
《东南大学学报(医学版)》
2025年第4期525-533,共9页
Journal of Southeast University(Medical Science Edition)
基金
国家自然科学基金资助项目(81902334,81972555)
江苏省卫生健康委面上项目(2023-X0462)。
关键词
肺腺癌
循环肿瘤细胞
LASSO回归分析
差异基因表达
预后模型
lung adenocarcinoma
circulating tumor cells
LASSO regression
differentially expressed genes
prognostic model
