Identification of novel prognostic autoantibodies in diffuse large B‐cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone via a high‐throughput antigen microarray

Background R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is a standard first‐line treatment for diffuse large B‐cell lymphoma (DLBCL). However, 20%–40% of patients survive less than 5 years. Novel prognostic biomarkers remain in demand. Methods Baseline plasma au...

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Bibliographic Details
Published in:Cancer 2024-04, Vol.130 (8), p.1257-1269
Main Authors: Dai, Liyuan, Chen, Haizhu, Tan, Qiaoyun, Wang, Yanrong, Li, Lin, Lou, Ning, Fan, Guangyu, Xie, Tongji, Luo, Rongrong, Wang, Shasha, Zhou, Yu, Zhong, Qiaofeng, Yao, Jiarui, Zhang, Zhishang, Tang, Le, Shi, Yuankai, Han, Xiaohong
Format: Article
Language:English
Subjects:
Antigens
Autoantibodies
autoantibody
Biomarkers
Cyclophosphamide
diffuse large B‐cell lymphoma
DNA microarrays
Doxorubicin
Gene expression
Immunohistochemistry
Lymphoma
Prednisone
prognostic biomarkers
protein microarray
Proteins
Regression analysis
Regression models
Risk
Rituximab
Survival
Vincristine
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Summary:Background R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is a standard first‐line treatment for diffuse large B‐cell lymphoma (DLBCL). However, 20%–40% of patients survive less than 5 years. Novel prognostic biomarkers remain in demand. Methods Baseline plasma autoantibodies (AAbs) were assessed in 336 DLBCLs. In the discovery phase (n = 20), a high‐density antigen microarray (∼21,000 proteins) was used to expound AAb profiles. In the verification phase (n = 181), with a DLBCL‐focused microarray, comparative results based on event‐free survival at 24 months (EFS24) and lasso Cox regression models of progression‐free survival (PFS) and overall survival (OS) were integrated to identify potential biomarkers. They were further validated by enzyme‐linked immunosorbent assay in validation phase 1 (n = 135) and a dynamic cohort (n = 12). In validation phase 2, a two‐AAb‐based risk score was established. They were further validated in an immunohistochemistry cohort (n = 55) and four independent Gene Expression Omnibus datasets (n = 1598). Results Four AAbs (CREB1, N4BP1, UBAP2, and DEAF1) were identified that showed associations with EFS24 status (p 
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.35158