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.
MDPI (Multidisciplinary Digital Publishing Institute)
Funding / projects:
COST (European Coopera-tion in Science and Technology) Action CA17104 STRATAGEM—“New diagnostic and therapeutictools against multidrug-resistant tumours”
Medical Faculty of the Military Medical Academy, University of Defense in Belgrade, Serbia(MFVMA01/23–25)
TY - JOUR
AU - Mandić, Danijela
AU - Nežić, Lana
AU - Amdžić, Ljiljana
AU - Vojinović, Nataša
AU - Gajanin, Radoslav
AU - Popović, Miroslav
AU - Đeri, Jugoslav
AU - Todorović Balint, Milena
AU - Dumanović, Jelena
AU - Milovanović, Zoran
AU - Grujić-Milanović, Jelica
AU - Škrbić, Ranko
AU - Jaćević, Vesna
PY - 2023
UR - http://rimi.imi.bg.ac.rs/handle/123456789/1343
AB - 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.
PB - MDPI (Multidisciplinary Digital Publishing Institute)
T2 - Cancers
T2 - Cancers
T1 - Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment
IS - 16
SP - 4106
VL - 15
DO - 10.3390/cancers15164106
ER -
@article{
author = "Mandić, Danijela and Nežić, Lana and Amdžić, Ljiljana and Vojinović, Nataša and Gajanin, Radoslav and Popović, Miroslav and Đeri, Jugoslav and Todorović Balint, Milena and Dumanović, Jelena and Milovanović, Zoran and Grujić-Milanović, Jelica and Škrbić, Ranko and Jaćević, Vesna",
year = "2023",
abstract = "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.",
publisher = "MDPI (Multidisciplinary Digital Publishing Institute)",
journal = "Cancers, Cancers",
title = "Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment",
number = "16",
pages = "4106",
volume = "15",
doi = "10.3390/cancers15164106"
}
Mandić, D., Nežić, L., Amdžić, L., Vojinović, N., Gajanin, R., Popović, M., Đeri, J., Todorović Balint, M., Dumanović, J., Milovanović, Z., Grujić-Milanović, J., Škrbić, R.,& Jaćević, V.. (2023). Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment. in Cancers
MDPI (Multidisciplinary Digital Publishing Institute)., 15(16), 4106.
https://doi.org/10.3390/cancers15164106
Mandić D, Nežić L, Amdžić L, Vojinović N, Gajanin R, Popović M, Đeri J, Todorović Balint M, Dumanović J, Milovanović Z, Grujić-Milanović J, Škrbić R, Jaćević V. Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment. in Cancers. 2023;15(16):4106.
doi:10.3390/cancers15164106 .
Mandić, Danijela, Nežić, Lana, Amdžić, Ljiljana, Vojinović, Nataša, Gajanin, Radoslav, Popović, Miroslav, Đeri, Jugoslav, Todorović Balint, Milena, Dumanović, Jelena, Milovanović, Zoran, Grujić-Milanović, Jelica, Škrbić, Ranko, Jaćević, Vesna, "Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment" in Cancers, 15, no. 16 (2023):4106,
https://doi.org/10.3390/cancers15164106 . .
