Immune-phenotyping and transcriptomic profiling of blood monocytes from patients with breast cancer under neoadjuvant chemotherapy

Introduction. Chemotherapy is a common treatment for breast cancer. Chemotherapeutic drugs effect blood monocytes, which are major contributors to cancer pathogenesis. However, to date, pro-tumor or anti-tumor programming by chemotherapy of monocytes is controversial.Aim. To characterize changes in...

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Main Authors: M. R. Patysheva, M. N. Stakheyeva, E. S. Grigoryeva, P. S. Iamshchikov, I. V. Larionova, А. A. Budnickya, N. A. Tarabanovskaya, N. V. Cherdyntseva, J. G. Kzhyshkowska
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Language:Russian
Published: ABV-press 2024-04-01
Series:Успехи молекулярной онкологии
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Online Access:https://umo.abvpress.ru/jour/article/view/650
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author M. R. Patysheva
M. N. Stakheyeva
E. S. Grigoryeva
P. S. Iamshchikov
I. V. Larionova
А. A. Budnickya
N. A. Tarabanovskaya
N. V. Cherdyntseva
J. G. Kzhyshkowska
author_facet M. R. Patysheva
M. N. Stakheyeva
E. S. Grigoryeva
P. S. Iamshchikov
I. V. Larionova
А. A. Budnickya
N. A. Tarabanovskaya
N. V. Cherdyntseva
J. G. Kzhyshkowska
author_sort M. R. Patysheva
collection DOAJ
description Introduction. Chemotherapy is a common treatment for breast cancer. Chemotherapeutic drugs effect blood monocytes, which are major contributors to cancer pathogenesis. However, to date, pro-tumor or anti-tumor programming by chemotherapy of monocytes is controversial.Aim. To characterize changes in phenotypic and transcriptomic profiles of monocytes of breast cancer patients before and after chemotherapeutic treatment.Materials and methods. In a cohort of 50 breast cancer patients, monocyte populations were identified based on their expression of CD14, CD16, CD163, and HLA-DR evaluated by flow cytometry before and after neoadjuvant chemotherapy. Bulk RNA sequencing was adopted to explore the transcriptomic profile of CD14+ monocytes before and after treatment. After treatment, we observed an increase in the activity of signaling pathways related to lipid metabolism and intracellular transport of vesicles from the endoplasmic reticulum, against the background of a decreased response to exposure to interferon γ and interferon α, and foreign molecules (exogenous nucleic acids, viruses and bacteria).Results. In breast cancer patients, neoadjuvant chemotherapy decreased in CD14+16+HLA-DR+ monocytes. Under cytostatic treatment, increased gene expression of MGLL, NR4A2, UCK1, YOD1, ABCA2, PAPSS2, ATP10 (log2FoldChange ≥0.8; false discovery rate (FDR) ≤0.01) and decreased gene expression of KPNA2, ERCC4, JAGN1, RUBCNL, SMYD4, B3GALT4 (log2FoldChange ≥0.8; FDR ≤0.01) were observed in monocytes of patients. Using discriminant analysis, the relative numbers of CD14+16–, CD14+16+, CD14-16+, CD14+16-HLA-DR+, CD14+16+HLA-DR+ and CD14–16+HLA-DR+ monocytes in the blood were found to be valuable in predicting response to neoadjuvant chemotherapy.Conclusion. Thus, association of blood monocytes with chemotherapeutic treatment in breast cancer was revealed.
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spelling doaj-art-39b45cec6d9b49209bf7f34cbc9bca082025-08-04T14:04:37ZrusABV-pressУспехи молекулярной онкологии2313-805X2413-37872024-04-01111798910.17650/2313-805X-2024-11-1-79-89319Immune-phenotyping and transcriptomic profiling of blood monocytes from patients with breast cancer under neoadjuvant chemotherapyM. R. Patysheva0M. N. Stakheyeva1E. S. Grigoryeva2P. S. Iamshchikov3I. V. Larionova4А. A. Budnickya5N. A. Tarabanovskaya6N. V. Cherdyntseva7J. G. Kzhyshkowska8Cancer Research Institute of Tomsk National Research Medical Center of the Russian Academy of Sciences; National Research Tomsk State UniversityCancer Research Institute of Tomsk National Research Medical Center of the Russian Academy of SciencesCancer Research Institute of Tomsk National Research Medical Center of the Russian Academy of SciencesCancer Research Institute of Tomsk National Research Medical Center of the Russian Academy of Sciences; National Research Tomsk State UniversityCancer Research Institute of Tomsk National Research Medical Center of the Russian Academy of Sciences; National Research Tomsk State UniversityNational Research Tomsk State UniversityCancer Research Institute of Tomsk National Research Medical Center of the Russian Academy of SciencesCancer Research Institute of Tomsk National Research Medical Center of the Russian Academy of Sciences; National Research Tomsk State UniversityNational Research Tomsk State UniversityIntroduction. Chemotherapy is a common treatment for breast cancer. Chemotherapeutic drugs effect blood monocytes, which are major contributors to cancer pathogenesis. However, to date, pro-tumor or anti-tumor programming by chemotherapy of monocytes is controversial.Aim. To characterize changes in phenotypic and transcriptomic profiles of monocytes of breast cancer patients before and after chemotherapeutic treatment.Materials and methods. In a cohort of 50 breast cancer patients, monocyte populations were identified based on their expression of CD14, CD16, CD163, and HLA-DR evaluated by flow cytometry before and after neoadjuvant chemotherapy. Bulk RNA sequencing was adopted to explore the transcriptomic profile of CD14+ monocytes before and after treatment. After treatment, we observed an increase in the activity of signaling pathways related to lipid metabolism and intracellular transport of vesicles from the endoplasmic reticulum, against the background of a decreased response to exposure to interferon γ and interferon α, and foreign molecules (exogenous nucleic acids, viruses and bacteria).Results. In breast cancer patients, neoadjuvant chemotherapy decreased in CD14+16+HLA-DR+ monocytes. Under cytostatic treatment, increased gene expression of MGLL, NR4A2, UCK1, YOD1, ABCA2, PAPSS2, ATP10 (log2FoldChange ≥0.8; false discovery rate (FDR) ≤0.01) and decreased gene expression of KPNA2, ERCC4, JAGN1, RUBCNL, SMYD4, B3GALT4 (log2FoldChange ≥0.8; FDR ≤0.01) were observed in monocytes of patients. Using discriminant analysis, the relative numbers of CD14+16–, CD14+16+, CD14-16+, CD14+16-HLA-DR+, CD14+16+HLA-DR+ and CD14–16+HLA-DR+ monocytes in the blood were found to be valuable in predicting response to neoadjuvant chemotherapy.Conclusion. Thus, association of blood monocytes with chemotherapeutic treatment in breast cancer was revealed.https://umo.abvpress.ru/jour/article/view/650monocytesbreast cancerrna-seqtranscriptomechemotherapyhla-dr
spellingShingle M. R. Patysheva
M. N. Stakheyeva
E. S. Grigoryeva
P. S. Iamshchikov
I. V. Larionova
А. A. Budnickya
N. A. Tarabanovskaya
N. V. Cherdyntseva
J. G. Kzhyshkowska
Immune-phenotyping and transcriptomic profiling of blood monocytes from patients with breast cancer under neoadjuvant chemotherapy
Успехи молекулярной онкологии
monocytes
breast cancer
rna-seq
transcriptome
chemotherapy
hla-dr
title Immune-phenotyping and transcriptomic profiling of blood monocytes from patients with breast cancer under neoadjuvant chemotherapy
title_full Immune-phenotyping and transcriptomic profiling of blood monocytes from patients with breast cancer under neoadjuvant chemotherapy
title_fullStr Immune-phenotyping and transcriptomic profiling of blood monocytes from patients with breast cancer under neoadjuvant chemotherapy
title_full_unstemmed Immune-phenotyping and transcriptomic profiling of blood monocytes from patients with breast cancer under neoadjuvant chemotherapy
title_short Immune-phenotyping and transcriptomic profiling of blood monocytes from patients with breast cancer under neoadjuvant chemotherapy
title_sort immune phenotyping and transcriptomic profiling of blood monocytes from patients with breast cancer under neoadjuvant chemotherapy
topic monocytes
breast cancer
rna-seq
transcriptome
chemotherapy
hla-dr
url https://umo.abvpress.ru/jour/article/view/650
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AT esgrigoryeva immunephenotypingandtranscriptomicprofilingofbloodmonocytesfrompatientswithbreastcancerunderneoadjuvantchemotherapy
AT psiamshchikov immunephenotypingandtranscriptomicprofilingofbloodmonocytesfrompatientswithbreastcancerunderneoadjuvantchemotherapy
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