Lung Microbiome Differentially Impacts Survival of Patients with Non-Small Cell Lung Cancer Depending on Tumor Stroma Phenotype

Ковалева, О. В.; Podlesnaya, P. A.; Рашидова, М. А.; Samoilova, Daria V.; Petrenko, Anatoly; Zborovskaya, I. B.; Мочальникова, В В; Kataev, Vladimir; Khlopko, Yuriy A.; Плотников, А. О.; Gratchev, Alexei

doi:10.3390/biomedicines8090349

Cited by 37 publications

(24 citation statements)

References 38 publications

(45 reference statements)

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“…Necrotic areas were ignored. The content of CD68, PU.1, CD163, CD3, CD8, FoxP3, CD20, CD56 and CD66b in tumor stroma was expressed as the median of the cell number in one microscopic field [ 22 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

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

Ковалева¹,

Podlesnaya²,

Sorokin³

et al. 2022

Biomedicines

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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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Section: Methodsmentioning

confidence: 99%

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

Ковалева¹,

Podlesnaya²,

Sorokin³

et al. 2022

Biomedicines

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“…Samples with scores 0–1 for CD206, CD8, and FoxP3 were combined in a group with low expression and samples with scores 2–3 were combined in a group with high expression. For CD68, CD163, CHID1, and CD3, samples with scores 0, 1, and 2 were combined in a group with low expression and samples with a score of 3 represented a group with high expression [ 32 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

CHID1 Is a Novel Prognostic Marker of Non-Small Cell Lung Cancer

Ковалева¹,

Рашидова²,

Samoilova³

et al. 2021

IJMS

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There is an urgent need for identification of new prognostic markers and therapeutic targets for non-small cell lung cancer (NSCLC). In this study, we evaluated immune cells markers in 100 NSCLC specimens. Immunohistochemical analysis revealed no prognostic value for the markers studied, except CD163 and CD206. At the same time, macrophage markers iNOS and CHID1 were found to be expressed in tumor cells and associated with prognosis. We showed that high iNOS expression is a marker of favorable prognosis for squamous cell lung carcinoma (SCC), and NSCLC in general. Similarly, high CHID1 expression is a marker of good prognosis in adenocarcinoma and in NSCLC in general. Analysis of prognostic significance of a high CHID1/iNOS expression combination showed favorable prognosis with 20 months overall survival of patients from the low CHID1/iNOS expression group. For the first time, we demonstrated that CHID1 can be expressed by NSCLC cells and its high expression is a marker of good prognosis for adenocarcinoma and NSCLC in general. At the same time, high expression of iNOS in tumor cells is a marker of good prognosis in SCC. When used in combination, CHID1 and iNOS show a very good prognostic capacity for NSCLC. We suggest that in the case of lung cancer, tumor-associated macrophages are likely ineffective as a therapeutic target. At the same time, macrophage markers expressed by tumor cells may be considered as targets for anti-tumor therapy or, as in the case of CHID1, as potential anti-tumor agents.

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“…There are also existing microbes in cancer tumors [9], and the microbes in cancer tissues are very different from those in non-tumor tissues [10,11]. Many studies have con rmed that there are many microbes in the lung tissue [12][13][14][15]. Existing studies have shown that gut microbes can affect the composition of lung microbes through gut-lung axis, thereby affecting the development of LC [16].…”

Section: Introductionmentioning

confidence: 99%

Alternations of fecal microbes and lung tissue microbes in Lung Cancer patients is more Identical than that of sputum

Kun

Zhang

2022

Preprint

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Microbiome in the human body environment is related to the occurrence of a variety of disease phenotypes. In this project, we collected lung tissue, feces and sputum from three Bioprojects of NCBI related to lung cancer (LC). Each project contains LC cases and lung normal (LN) controls. Those three projects contain a total of 339 samples of 16s rRNA sequencing data. By analyzing the composition of microbes in the three environments, and predicting their functions we found that compared with sputum, the ecological environment of fecal microbe is closer to tissue microbes in terms of evolutionary relationship. We used Picrust2 to predict the differential microbe function of lung cancer (LC) and the control (Lung Normal, LN) groups in the three environments, and found that at the microbe genetic level, compared to feces and sputum, sputum and tissues, feces and tissues have more common Differential genes, at the level of differential enzyme genes and differential pathways, feces and tissues have more common differences compared to feces and sputum, sputum and tissues. The results indicated that the activation of marker genus in sputum and feces and significantly changed pathways has an opposite trend, and there are many pathways contributing to glycolysis are correlated with marker genus. Patients with LC has potential to regulate the microbe composition of feces, tissues and sputum by regulating glycolysis metabolism.

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Lung Microbiome Differentially Impacts Survival of Patients with Non-Small Cell Lung Cancer Depending on Tumor Stroma Phenotype

Cited by 37 publications

References 38 publications

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

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

CHID1 Is a Novel Prognostic Marker of Non-Small Cell Lung Cancer

Alternations of fecal microbes and lung tissue microbes in Lung Cancer patients is more Identical than that of sputum

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