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

IF 5.1 2区医学 Q1 ONCOLOGY

Cancer Pub Date : 2023-12-22 DOI:10.1002/cncr.35158

Liyuan Dai MBBS, Haizhu Chen MD, Qiaoyun Tan MD, Yanrong Wang MM, Lin Li MD, Ning Lou MBBS, Guangyu Fan MBBS, Tongji Xie MM, Rongrong Luo MD, Shasha Wang MD, Yu Zhou MD, Qiaofeng Zhong MD, Jiarui Yao MBBS, Zhishang Zhang MBBS, Le Tang MBBS, Yuankai Shi MD, Xiaohong Han MD

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引用次数: 0

Abstract

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 < .05) and superior PFS and OS (p < .05). A novel risk score model based on CREB1 and N4BP1 AAbs was developed to predict PFS with areas under the curve of 0.72, 0.71, 0.76, and 0.82 at 1, 3, 5, and 7 years, respectively, in DLBCL treated with R-CHOP independent of the International Prognostic Index (IPI) and provided significant additional recurrence risk discrimination (p < .05) for the IPI. CREB1 and N4BP1 proteins and messenger RNAs were also associated with better PFS and OS (p < .05).

Conclusions

This study identified a novel prognostic panel of CREB1, N4BP1, DEAF1, and UBAP2 AAbs that is independent of the IPI in DLBCL.

Abstract Image

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通过高通量抗原芯片鉴定利妥昔单抗加环磷酰胺、多柔比星、长春新碱和泼尼松治疗弥漫大B细胞淋巴瘤的新型预后自身抗体。

背景：R-CHOP（利妥昔单抗加环磷酰胺、多柔比星、长春新碱和泼尼松）是弥漫大 B 细胞淋巴瘤（DLBCL）的标准一线治疗方法。然而，20%-40%的患者存活时间不足5年。目前仍需要新的预后生物标志物：方法：对336例DLBCL患者的血浆自身抗体（AAbs）进行基线评估。在发现阶段（n = 20），使用高密度抗原芯片（∼21,000 个蛋白质）来阐述 AAb 特征。在验证阶段（n = 181），使用以 DLBCL 为重点的微阵列，整合了基于 24 个月无事件生存期（EFS24）的比较结果以及无进展生存期（PFS）和总生存期（OS）的 lasso Cox 回归模型，以确定潜在的生物标记物。在验证阶段 1（n = 135）和动态队列（n = 12）中，通过酶联免疫吸附试验进一步验证了这些生物标记物。在验证阶段 2，建立了基于两种抗体的风险评分。在免疫组化队列（n = 55）和四个独立的基因表达总库数据集（n = 1598）中对它们进行了进一步验证：结果：发现了四种AAbs（CREB1、N4BP1、UBAP2和DEAF1）与EFS24状态相关（p 结论：该研究发现了一种新的预后评估方法：这项研究发现了一个由 CREB1、N4BP1、DEAF1 和 UBAP2 AAbs 组成的新型预后面板，它与 DLBCL 的 IPI 无关。

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来源期刊

Cancer 医学-肿瘤学

CiteScore

13.10

自引率

3.20%

发文量

480

审稿时长

2-3 weeks

期刊介绍： The CANCER site is a full-text, electronic implementation of CANCER, an Interdisciplinary International Journal of the American Cancer Society, and CANCER CYTOPATHOLOGY, a Journal of the American Cancer Society. CANCER publishes interdisciplinary oncologic information according to, but not limited to, the following disease sites and disciplines: blood/bone marrow; breast disease; endocrine disorders; epidemiology; gastrointestinal tract; genitourinary disease; gynecologic oncology; head and neck disease; hepatobiliary tract; integrated medicine; lung disease; medical oncology; neuro-oncology; pathology radiation oncology; translational research