长非编码RNA AL445524.1相关肝细胞癌预后模型的构建及其对肝癌细胞恶性表型的影响  

Construction of a prognostic model of hepatocellular carcinoma associated with lncRNA AL445524.1 and its effect on the malignant phenotype of hepatocellular carcinoma cells

作　　者：薛小芳[1] 钟玉全[1] 李欣阳 Xue Xiaofang;Zhong Yuquan;Li Xinyang(Department of Gastroenterology,First People's Hospital of Neijiang,Sichuan Province,Neijiang 641000,China;School of Clinical Medicine,Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]四川省内江市第一人民医院消化内科,内江641000 [2]成都医学院临床医学院,成都610500

出　　处：《国际肿瘤学杂志》2024年第11期696-705,共10页Journal of International Oncology

摘　　要：目的探讨长非编码RNA(lncRNA)AL445524.1在肝细胞癌(HCC)中的预后评估价值及对肝癌细胞的调控作用。方法基于TCGA数据库利用生物信息学分析AL445524.1在HCC中的表达水平,以AL445524.1表达水平的中位数作为临界值,将343例HCC患者分为高表达组和低表达组,采用Kaplan-Meier曲线进行生存分析;采用单因素和多因素Cox比例风险回归模型分析AL445524.1表达和其他临床特征与患者预后的关系,筛选HCC患者预后的独立危险因素,基于多因素分析结果,将数据完整的患者以7∶3的比例按照随机数字表法分为测试集(n=215)和训练集(n=92),并以此构建HCC的列线图预后预测模型,绘制受试者操作特征(ROC)曲线,计算曲线下面积(AUC),分析和验证预测模型的预测性能;对AL445524.1调控的差异基因进行功能富集分析;采用RT-PCR法检测肝癌细胞中AL445524.1表达水平。将人肝癌细胞株HCCLM3分为si-AL445524.1-1、si-AL445524.1-2、si-AL445524.1-3、si-NC组。通过CCK-8实验检测细胞增殖能力;细胞划痕及Transwell实验检测细胞迁移和侵袭能力;流式细胞术检测细胞凋亡情况。结果AL445524.1在肝癌组织中的表达显著高于癌旁组织(4.38±1.26比2.08±0.45,t=24.58,P<0.001)。Kaplan-Meier生存分析显示,AL445524.1高表达组(n=170)HCC患者的5年总生存(OS)率为37.37%,低表达组(n=173)患者为58.38%,差异有统计学意义(χ^(2)=8.83,P=0.003)。多因素分析显示,肿瘤复发(HR=2.58,95%CI为1.64~4.07,P<0.001)、临床分期(HR=2.49,95%CI为1.63~3.81,P<0.001)及AL445524.1表达(HR=1.23,95%CI为1.06~1.41,P=0.010)均是HCC患者预后的独立影响因素。基于肿瘤复发、临床分期、AL445524.1表达构建列线图预后预测模型,模型风险评分=0.774×肿瘤复发+0.753×临床分期+0.231×AL445524.1。预测模型C-index在训练集、测试集及全集中分别为0.726、0.660及0.678。ROC曲线分析显示,预测模型预测训练集、测试集及全集患者的1年OS率的AUC值�Objective To explore the prognostic value of long non-coding RNA(lncRNA)AL445524.1 in hepatocellular carcinoma(HCC)and its regulatory effect on liver cancer cells.Methods Based on the TCGA database,bioinformatics analysis was conducted to assess the expression levels of AL445524.1 in HCC.Using the median expression level of AL445524.1 as the cut-off value,343 HCC patients were divided into high expression group and low expression group.Survival analysis was performed using Kaplan-Meier curves.Univariate and multivariate Cox proportional hazards regression models were employed to analyze the relationship between AL445524.1 expression,other clinical characteristics,and patients'prognosis,identifying independent risk factors for the prognosis of HCC patients.Based on the results of the multivariate analysis,patients with complete data were randomly divided into a testing set(n=215)and a training set(n=92)in a 7∶3 ratio using a random number table method,and a nomogram prognostic prediction model for HCC was constructed.Receiver operator characteristic(ROC)curves were plotted to calculate the area under the curve(AUC)to analyze and validate the predictive performance of the model.Functional enrichment analysis was conducted on the differentially expressed genes regulated by AL445524.1.The expression level of AL445524.1 in liver cancer cells was detected using RT-PCR.Human hepatoma cell lines HCCLM3 were divided into si-AL445524.1-1,si-AL445524.1-2,si-AL445524.1-3 and si-NC groups.The CCK-8 assay was used to assess cell proliferation capability;cell scratch and Transwell assays were performed to evaluate cell migration and invasion abilities;and flow cytometry was utilized to detect cell apoptosis.Results The expression of AL445524.1 in liver cancer tissues was significantly higher than that in para-carcinoma tissues(4.38±1.26 vs.2.08±0.45,t=24.58,P<0.001).Kaplan-Meier survival analysis showed that the 5-year overall survival(OS)rate for HCC patients in high AL445524.1 expression group(n=170)was 37.37%,and that of

关 键 词：癌 肝细胞 lncRNA AL445524.1 生物信息学分析 细胞增殖 细胞运动 肿瘤浸润 细胞凋亡 

分 类 号：R73[医药卫生—肿瘤]