一种可预测弥漫大B细胞淋巴瘤患者生存的新型6基因预测模型

A novel six-gene based prognostic model for patients with diffuse large B-cell lymphoma

目的从分子生物学角度构建预测弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)预后的模型。方法从GEO和TCGA数据库下载相应的基因表达谱数据及临床数据,采用Lasso回归和多因素Cox回归构建基因预测模型,将基因模型与其他临床预后因素相结合构建列线图模型。结果本研究建立了基于6个基因(LNPEP、SNX20、GTPBP10、CALR、BDH1、C5orf30)的预测模型,该模型可将各个队列的患者分为高风险组及低风险组,训练集GSE10846及验证集GSE32918、NCICCR预测3年总生存率的AUC分别为0.722、0.758、0.693。基于该基因模型与年龄、亚型、治疗方案、ECOG、分期、结外部位数量等临床因素构建的列线图模型预测DLBCL患者3年总生存率的AUC在GSE10846数据集为0.796,校准图一致性良好。GO及KEGG富集分析显示,该模型的基因主要与DNA复制和修复、蛋白加工、细胞周期、病毒致癌等生物功能及通路相关。结论本研究成功构建了可预测DLBCL患者生存的基因预测模型,与临床因素结合,能更准确地评估患者的预后。

Objective To develop a prognosis model for diffuse large B-cell lymphoma(DLBCL)based on the perspective of molecular biology.Methods The DLBCL gene-expression data and clinical information were downloaded from the GEO and TCGA databases.The Gene prediction model was constructed by using Lasso regression and multivariable Cox regression,and the gene model was combined with other clinical prognostic factors to construct the nomogram model.Results The prediction model was established by six genes(LNPEP、SNX20、GTPBP10、CALR、BDH1、C5orf30)which could divide patients in each cohort into high-risk group and low-risk group.The AUC of 3-year overall survival rate in GSE10846,GSE32918 and NCICCR were 0.722,0.758 and 0.693,respectively.Based on this gene model and the clinical factors such as age,subtype,therapeutic schedule,ECOG,stage,and number of junction external locus,we concluded that the AUC of 3-year overall survival rate in GSE10846 was 0.796,the calibration plot showed good consistency.The GO and KEGG enrichment analysis showed that the genes of this model were mainly related to the biological functions and pathways such as DNA replication,repair,protein processing,cell cycle and viral carcinogenesis.Conclusions A gene prediction model is constructed,which can be used to predict the survival of DLBCL patients.When combined with clinical factors,the model can be better used to evaluate the prognosis of patients.