Machine learning-based classification of diffuse large B-cell lymphoma patients by eight gene expression profiles.

Abstract

Gene expression profiling (GEP) had divided the diffuse large B-cell lymphoma (DLBCL) into molecular subgroups: germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassified (UC) subtype. However, this classification with prognostic significance was not applied into clinical practice since there were more than 1000 genes to detect and interpreting was difficult. To classify cancer samples validly, eight significant genes (MYBL1, LMO2, BCL6, MME, IRF4, NFKBIZ, PDE4B, and SLA) were selected in 414 patients treated with CHOP/R-CHOP chemotherapy from Gene Expression Omnibus (GEO) data sets. Cutoffs for each gene were obtained using receiver-operating characteristic curves (ROC) new model based on the support vector machine (SVM) estimated the probability of membership into one of two subgroups: GCB and Non-GCB (ABC and UC). Furtherly, multivariate analysis validated the model in another two cohorts including 855 cases in all. As a result, patients in the training and validated cohorts were stratified into two subgroups with 94.0%, 91.0%, and 94.4% concordance with GEP, respectively. Patients with Non-GCB subtype had significantly poorer outcomes than that with GCB subtype, which agreed with the prognostic power of GEP classification. Moreover, the similar prognosis received in the low (0-2) and high (3-5) IPI scores group demonstrated that the new model was independent of IPI as well as GEP method. In conclusion, our new model could stratify DLBCL patients with CHOP/R-CHOP regimen matching GEP subtypes effectively.

• Authors: Shuangtao Zhao, Xiaoli Dong, Wenzhi Shen, Zhen Ye, Rong Xiang
• Journal: Cancer medicine (Cancer Med) Vol. 5 Issue 5 Pg. 837-52 (05 2016) ISSN: 2045-7634 [Electronic] United States
• PMID: 26869285 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• R-CHOP protocol
• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Aged
• Antibodies, Monoclonal, Murine-Derived (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cyclophosphamide (therapeutic use)
• Databases, Genetic
• Doxorubicin (therapeutic use)
• Female
• Gene Expression Profiling (methods)
• Genes, Neoplasm
• Germinal Center
• Humans
• Lymphoma, Large B-Cell, Diffuse (classification, diagnosis, drug therapy, genetics)
• Male
• Middle Aged
• Prednisone (therapeutic use)
• Prognosis
• ROC Curve
• Rituximab
• Sensitivity and Specificity
• Support Vector Machine
• Survival Analysis
• Treatment Outcome
• Vincristine (therapeutic use)