超表达MRP1/ABCC1、Survivin和BCRP/ABCC2预测了弥漫性大B细胞淋巴瘤对R-CHOP治疗的耐药性。
Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment.
发表日期:2023 Aug 15
作者:
Danijela Mandić, Lana Nežić, Ljiljana Amdžić, Nataša Vojinović, Radoslav Gajanin, Miroslav Popović, Jugoslav Đeri, Milena Todorović Balint, Jelena Dumanović, Zoran Milovanović, Jelica Grujić-Milanović, Ranko Škrbić, Vesna Jaćević
来源:
Experimental Hematology & Oncology
摘要:
大约40%的弥漫性大B细胞淋巴瘤(DLBCL)患者对一线R-CHOP方案出现治疗抗性。ATP结合盒(ABC)转运蛋白和生存因子可能在各种肿瘤的多药耐药性(MDR)中起到一定作用。本研究旨在调查ABC转运蛋白和生存因子的共表达是否与R-CHOP治疗反应有关。使用免疫组化分析从DLBCL患者获取的肿瘤标本中的Bcl-2、survivin、P-糖蛋白/ABCB1、MRP1/ABCC1和BCRP/ABCC2的表达情况,并根据治疗反应分为缓解、复发和(原发)难治组。所有患者接受了R-CHOP或等效治疗。Bcl-2与临床参数和除P-gp/ABCB1以外的所有生物标记物呈强正相关。MRP1/ABCC1、survivin和BCRP/ABCC2的过表达,即高免疫反应评分(IRS),分别检测到难治组和复发组(p < 0.05 vs 缓解)。而P-gp/ABCB1的IRS值较低。在难治组和复发组中,MRP1/ABCC1与survivin或BCRP/ABCC2之间存在显著相关性。在多元线性回归分析中,ECOG状态与MRP1/ABCC1或survivin以及BCRP/ABCG2显著相关,可预测R-CHOP治疗反应。DLBCL可能具有某些分子特征,如MRP1/ABCC1、survivin和BCRP/ABCC2的过表达,可预测对R-CHOP的耐药性。
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.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.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.DLBCL might harbor certain molecular signatures such as MRP1/ABCC1, survivin, and BCRP/ABCC2 overexpression that can predict resistance to R-CHOP.