基于细胞焦亡相关lncRNA构建甲状腺癌的预后模型研究

Study of prognostic model for thyroid cancer based on pyroptosis-related lncRNA

目的构建与细胞焦亡相关的长链非编码RNA(lncRNA)的甲状腺癌预后模型,并探索其预测价值。方法MSigDB数据库获得细胞焦亡相关的基因;癌症基因组图谱数据库中获取甲状腺癌患者的测序数据和临床资料并按1∶1的比例分为实验组和验证组;构建细胞焦亡相关基因和lncRNAs的共表达网络,并筛选相关系数|r|>0.5且P<0.001的lncRNAs。单因素Cox回归分析确定与预后相关lncRNAs。采用Lasso-Cox回归分析构建预后模型,计算实验组和验证组的风险评分。根据风险评分的受试者操作特征(ROC)曲线的最佳截断值将甲状腺癌患者分为高危组和低危组。利用Kaplan-Meier法进行生存分析。单因素和多因素Cox回归分析评估风险评分的独立预后价值。CIBERSORT分析肿瘤内的免疫浸润,分析风险评分与免疫检查点的相关性。结果本研究共得到1035个细胞焦亡相关的lncRNAs,最终筛选获得10个细胞焦亡相关lncRNAs。风险评分=1.197×AC092809.3+0.285×MIR3945HG+1.886×AL450326.1+1.457×AL360181.2+0.539×LMNTD2-AS1+1.090×AC069360.1-0.709×DOCK9-DT+0.841×GAPLINC+1.013×PARAL1+0.870×SLC12A5-AS1,ROC曲线获取的最佳截断值为0.050。高危组患者生存率低于低危组患者(P<0.01)。单因素及多因素Cox回归分析结果显示,风险评分的HR值分别为2.718(95%CI:2.039~3.624,P<0.01)、4.832(95%CI:1.562~14.945,P<0.01)。高危组患者中单核细胞、记忆B细胞和嗜酸性粒细胞增加,肥大细胞和调节性T细胞减少。风险评分与免疫检查点CD80、CD160和ADORA2A的表达有相关性。结论本研究构建的细胞焦亡相关lncRNAs预后模型对甲状腺癌的预后有良好的预测作用。

Objective To construct pyroptosis-related long non-coding RNA(lncRNA)prognostic model for thyroid cancer and explore its prognostic value.Methods The genes related to pyroptosis were obtained from MSigDB database;the sequencing data and clinical data of thyroid cancer patients were obtained from the Cancer Genome Atlas database and they were divided into experimental group and validation group at a ratio of 1∶1;the co-expression network of pyroptosis-related genes and lncRNAs was constructed,and the correction coefficient|r|>0.5 and P<0.001 lncRNAs were screened.Univariate Cox regression analysis identified lncRNAs associated with prognosis.Lasso-Cox regression analysis was used to construct a prognostic model,and the risk scores of experimental group and validation group were calculated.Thyroid cancer patients were divided into high-risk and low-risk groups according to the optimal cut-off value of the receiver operating characteristics(ROC)curve of the risk score.Survival analysis was performed using Kaplan-Meier method.Univariate and multivariate Cox regression analyses were used to evaluated the independent prognostic value of risk scores.Immune infiltration within the tumor was analyzed by CIBERSORT and the correlation between risk score and immune checkpoint was analyzed.Results In this study,a total of 1035 lncRNAs associated with pyroptosis were obtained,and 10 lncRNAs were finally screened.Risk score=1.197×AC092809.3+0.285×MIR3945HG+1.886×AL450326.1+1.457×AL360181.2+0.539×LMNTD2-AS1+1.090×AC069360.1-0.709×DOCK9-DT+0.841×GAPLINC+1.013×PARAL1+0.870×SLC12A5-AS1,the optimal cut-off value obtained by ROC curve was 0.050.The survival rate of high-risk group was lower than that of low-risk group(P<0.01).Univariate and multivariate Cox regression analysis showed that the HR values of risk scores were 2.718(95%CI:2.039-3.624,P<0.01)and 4.832(95%CI:1.562-14.945,P<0.01),respectively.In high-risk group,monocytes,memory B cells,and eosinophils increased,and mast cells and regulatory T cells decreased.Risk scores were associated with expression of CD80,CD160,and ADORA2A at immune checkpoints.Conclusion The prognostic-related lncRNAs prognostic model constructed in this study has good predictive value for the prognosis of thyroid cancer.