弥漫性大B细胞淋巴瘤的亚型分类及预后  

Cell-of-origin subtype classification and prognosis of diffuse large B-cell lymphoma based on variable importance analysis

作　　者：郝婷 高倩 郗彦凤[2] 关红卫 王彤 HAO Ting;GAO Qian;XI Yanfeng;GUAN Hongwei;WANG Tong(Department of Health Statistics,School of Public Health,Shanxi Medical University,Key Laboratory of Coal Environmental Pathogenicity and Prevention,Ministry of Education,Taiyuan 030001,China;Department of Pathology,Shanxi Provincial Cancer Hospital,Taiyuan 030013,China;School of Health Sciences and Human Performance,Ithaca College,New York 14850,USA)

机构地区：[1]山西医科大学公共卫生学院卫生统计学教研室,煤炭环境致病与防治教育部重点实验室,太原030001 [2]山西省肿瘤医院病理科,太原030013 [3]伊萨卡学院健康科学与人类行为学院,纽约14850

出　　处：《中华疾病控制杂志》2024年第2期198-202,208,共6页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(82073674,82204163);山西省基础研究计划(202203021212382)。

摘　　要：目的基因表达谱(gene expression profiling,GEP)是弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)细胞起源(cell-of-origin,COO)分类的金标准。本研究旨在建立一个基于GEP的简约模型来准确预测DLBCL的COO亚型并为其在临床上的应用提供参考。方法首先提出变量重要性评分方法以解决惩罚回归方法的不稳定性,随后基于这一策略提出了用于DLBCL分类的六基因模型。结果模型评估和模型比较均表明六基因模型表现良好,在训练数据集中,曲线下面积为0.999(95%CI:0.997~1.000),判别斜率为0.944(95%CI:0.920~0.966);在验证数据集中曲线下面积从0.910(95%CI:0.820~0.999)到1.000,判别斜率从0.506(95%CI:0.350~0.657)到0.927(95%CI:0.841~0.987)。结论六基因模型中的6个基因对DLBCL的分型和预后有重要的临床应用价值。基于变量重要性的基因排序为基因功能和靶向药物的进一步研究提供了参考依据。Objective Gene expression profiling(GEP)is the gold standard for cell-of-origin COO classification of diffuse large B-cell lymphoma(DLBCL).The aim of this study was to establish a GEP-based parsimony model to accurately predict the COO subtypes of DLBCL and provide a reference for its clinical application.Methods Genetic and clinical data from 6 DLBCL datasets in the GEO database were collected,and one dataset was used as the training set and the remaining five as the validation set.A variable importance analysis strategy based on penalized regression analysis was constructed to identify the optimal subset of variables,and a logistic regression analysis was performed to determine the six-gene model that was ultimately used for COO classification.Survival analysis was used to assess the relationship between the two COO subtypes predicted by the training and validation sets and clinical prognosis.Results The six-gene model predicted better in the training set[AUC(95%CI):0.999(0.997~1.000),discriminant slope and its 95%CI were 0.944(0.920~0.966)],and also showed better results in the validation set[AUC and its 95%CI fluctuated from 0.910(0.820~0.999)to 1.000,and the discriminant slope and its 95%CI fluctuated from 0.506(0.350~0.966)to 0.927(0.841~0.987)].The prognostic modeling showed that the six genetically predicted subtypes were risk predictors in both the training and validation sets(all P<0.05).Conclusions The six genes in the six-gene model have important clinical applications for the classification and prognosis of DLBCL.The gene ordering based on variable importance provides a reference basis for further-research on gene function and targeted drug research.

关 键 词：弥漫性大B细胞淋巴瘤 惩罚回归 预后 亚型分类 变量重要性分析 

分 类 号：R195.1[医药卫生—卫生统计学] R733.4[医药卫生—卫生事业管理]