Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients’ Survival: A Pilot Study

The identification of new prognostic markers of renal cell carcinoma (RCC) is an urgent problem in oncourology. To investigate the potential prognostic significance of tumor microbiome and stromal inflammatory markers, we studied a cohort of 66 patients with RCC (23 clear cell RCC, 19 papillary RCC...

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Main Authors: Olga V. Kovaleva, Polina Podlesnaya, Maxim Sorokin, Valeria Mochalnikova, Vladimir Kataev, Yuriy A. Khlopko, Andrey O. Plotnikov, Ivan S. Stilidi, Nikolay E. Kushlinskii, Alexei Gratchev
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/10/7/1516
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author Olga V. Kovaleva
Polina Podlesnaya
Maxim Sorokin
Valeria Mochalnikova
Vladimir Kataev
Yuriy A. Khlopko
Andrey O. Plotnikov
Ivan S. Stilidi
Nikolay E. Kushlinskii
Alexei Gratchev
author_facet Olga V. Kovaleva
Polina Podlesnaya
Maxim Sorokin
Valeria Mochalnikova
Vladimir Kataev
Yuriy A. Khlopko
Andrey O. Plotnikov
Ivan S. Stilidi
Nikolay E. Kushlinskii
Alexei Gratchev
author_sort Olga V. Kovaleva
collection DOAJ
description The identification of new prognostic markers of renal cell carcinoma (RCC) is an urgent problem in oncourology. To investigate the potential prognostic significance of tumor microbiome and stromal inflammatory markers, we studied a cohort of 66 patients with RCC (23 clear cell RCC, 19 papillary RCC and 24 chromophobe RCC). The microbiome was analyzed in tumor and normal tissue by 16S rRNA amplicon sequencing. Characterization of the tumor stroma was performed using immunohistochemistry. A significant difference in alpha diversity was demonstrated between normal kidney tissue and all types of RCC. Further, we demonstrated that the bacterial burden was higher in adjacent normal tissue than in a tumor. For the first time, we demonstrated a significant correlation between bacterial burden and the content of PU.1+ macrophages and CD66b+ neutrophils in kidney tumors. Tumors with high content of PU.1+ cells and CD66b+ cells in the stroma were characterized by a lower bacterial burden. In the tumors with high bacterial burden, the number of PU.1+ cells and CD66b+ was associated with a poor prognosis. The identified associations indicate the great prognostic potential of a combined tumor microbiome and stromal cell analysis.
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spelling doaj.art-1fa75ca5b73e4892b9d04d5a82eb61722023-12-01T21:55:39ZengMDPI AGBiomedicines2227-90592022-06-01107151610.3390/biomedicines10071516Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients’ Survival: A Pilot StudyOlga V. Kovaleva0Polina Podlesnaya1Maxim Sorokin2Valeria Mochalnikova3Vladimir Kataev4Yuriy A. Khlopko5Andrey O. Plotnikov6Ivan S. Stilidi7Nikolay E. Kushlinskii8Alexei Gratchev9N.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, RussiaInstitute for Cellular and Intracellular Symbiosis of the Ural Branch of the Russian Academy of Sciences, 460000 Orenburg, RussiaInstitute for Cellular and Intracellular Symbiosis of the Ural Branch of the Russian Academy of Sciences, 460000 Orenburg, RussiaInstitute for Cellular and Intracellular Symbiosis of the Ural Branch of the Russian Academy of Sciences, 460000 Orenburg, RussiaN.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, RussiaThe identification of new prognostic markers of renal cell carcinoma (RCC) is an urgent problem in oncourology. To investigate the potential prognostic significance of tumor microbiome and stromal inflammatory markers, we studied a cohort of 66 patients with RCC (23 clear cell RCC, 19 papillary RCC and 24 chromophobe RCC). The microbiome was analyzed in tumor and normal tissue by 16S rRNA amplicon sequencing. Characterization of the tumor stroma was performed using immunohistochemistry. A significant difference in alpha diversity was demonstrated between normal kidney tissue and all types of RCC. Further, we demonstrated that the bacterial burden was higher in adjacent normal tissue than in a tumor. For the first time, we demonstrated a significant correlation between bacterial burden and the content of PU.1+ macrophages and CD66b+ neutrophils in kidney tumors. Tumors with high content of PU.1+ cells and CD66b+ cells in the stroma were characterized by a lower bacterial burden. In the tumors with high bacterial burden, the number of PU.1+ cells and CD66b+ was associated with a poor prognosis. The identified associations indicate the great prognostic potential of a combined tumor microbiome and stromal cell analysis.https://www.mdpi.com/2227-9059/10/7/1516renal cell carcinomaprognosisPU.1microbiomemacrophagestroma
spellingShingle Olga V. Kovaleva
Polina Podlesnaya
Maxim Sorokin
Valeria Mochalnikova
Vladimir Kataev
Yuriy A. Khlopko
Andrey O. Plotnikov
Ivan S. Stilidi
Nikolay E. Kushlinskii
Alexei Gratchev
Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients’ Survival: A Pilot Study
Biomedicines
renal cell carcinoma
prognosis
PU.1
microbiome
macrophage
stroma
title Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients’ Survival: A Pilot Study
title_full Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients’ Survival: A Pilot Study
title_fullStr Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients’ Survival: A Pilot Study
title_full_unstemmed Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients’ Survival: A Pilot Study
title_short Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients’ Survival: A Pilot Study
title_sort macrophage phenotype in combination with tumor microbiome composition predicts rcc patients survival a pilot study
topic renal cell carcinoma
prognosis
PU.1
microbiome
macrophage
stroma
url https://www.mdpi.com/2227-9059/10/7/1516
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