文章：

MRP1/ABCC1、Survivin及BCRP/ABCC2的过表达预示弥漫性大B细胞淋巴瘤对R-CHOP方案耐药

Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment

原文发布日期：15 August 2023

DOI: 10.3390/cancers15164106

类型: Article

开放获取: 是

英文摘要：

Background: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience treatment resistance to the first-line R-CHOP regimen. ATP binding cassette (ABC) transporters and survivin might play a role in multidrug resistance (MDR) in various tumors. The aim was to investigate if the coexpression of ABC transporters and survivin was associated with R-CHOP treatment response. Methods: The expression of Bcl-2, survivin, P-glycoprotein/ABCB1, MRP1/ABCC1, and BCRP/ABCC2 was analyzed using immunohistochemistry in tumor specimens obtained from patients with DLBCL, and classified according to the treatment response as Remission, Relapsed, and (primary) Refractory groups. All patients received R-CHOP or equivalent treatment. Results: Bcl-2 was in strong positive correlation with clinical parameters and all biomarkers except P-gp/ABCB1. The overexpression of MRP1/ABCC1, survivin, and BCRP/ABCC2 presented as high immunoreactive scores (IRSs) was detected in the Refractory and Relapsed groups (p< 0.05 vs. Remission), respectively, whereas the IRS of P-gp/ABCB1 was low. Significant correlations were found among either MRP1/ABCC1 and survivin or BCRP/ABCC2 in the Refractory and Relapsed groups, respectively. In multiple linear regression analysis, ECOG status along with MRP1/ABCC1 or survivin and BRCP/ABCG2 was significantly associated with the prediction of the R-CHOP treatment response. Conclusions: DLBCL might harbor certain molecular signatures such as MRP1/ABCC1, survivin, and BCRP/ABCC2 overexpression that can predict resistance to R-CHOP.

摘要翻译： 

背景：约40%的弥漫性大B细胞淋巴瘤（DLBCL）患者对一线R-CHOP方案产生治疗抵抗。ATP结合盒（ABC）转运蛋白和生存素可能在多种肿瘤的多药耐药（MDR）中发挥作用。本研究旨在探讨ABC转运蛋白与生存素的共表达是否与R-CHOP治疗反应相关。方法：通过免疫组织化学法分析DLBCL患者肿瘤标本中Bcl-2、生存素、P-糖蛋白/ABCB1、MRP1/ABCC1和BCRP/ABCG2的表达水平，并根据治疗反应将患者分为缓解组、复发组和（原发性）难治组。所有患者均接受R-CHOP或等效方案治疗。结果：Bcl-2与临床参数及除P-gp/ABCB1外的所有生物标志物均呈强正相关。在难治组和复发组中分别检测到MRP1/ABCC1、生存素和BCRP/ABCG2的高免疫反应评分（IRS）过表达（与缓解组相比p<0.05），而P-gp/ABCB1的IRS较低。在难治组和复发组中，MRP1/ABCC1与生存素、BCRP/ABCG2分别存在显著相关性。多元线性回归分析显示，ECOG状态联合MRP1/ABCC1或生存素及BRCP/ABCG2对预测R-CHOP治疗反应具有显著意义。结论：DLBCL可能具有特定的分子特征，如MRP1/ABCC1、生存素和BCRP/ABCG2过表达，这些特征可预测对R-CHOP方案的耐药性。

原文链接：

Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment