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

被引:29
作者
Kovaleva, Olga [1 ]
Podlesnaya, Polina [1 ]
Rashidova, Madina [1 ]
Samoilova, Daria [1 ]
Petrenko, Anatoly [1 ]
Zborovskaya, Irina [1 ]
Mochalnikova, Valeria [1 ]
Kataev, Vladimir [2 ]
Khlopko, Yuri [2 ]
Plotnikov, Andrey [2 ]
Gratchev, Alexei [1 ]
机构
[1] NN Blokhin Natl Med Res Ctr Oncol, Moscow 115478, Russia
[2] Russian Acad Sci, Inst Cellular & Intracellular Symbiosis, Ural Branch, Orenburg 460000, Russia
基金
俄罗斯基础研究基金会;
关键词
non-small cell lung cancer; prognosis; iNOS; microbiome; macrophage; stroma; Treg; MACROPHAGES; EXPRESSION; SEQUENCES; ISLETS;
D O I
10.3390/biomedicines8090349
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The link between a lung tumor and the lung microbiome is a largely unexplored issue. To investigate the relationship between a lung microbiome and the phenotype of an inflammatory stromal infiltrate, we studied a cohort of 89 patients with non-small cell lung cancer. The microbiome was analyzed in tumor and adjacent normal tissue by 16S rRNA amplicon sequencing. Characterization of the tumor stroma was done using immunohistochemistry. We demonstrated that the bacterial load was higher in adjacent normal tissue than in a tumor (p = 0.0325) with similar patterns of taxonomic structure and alpha diversity. Lung adenocarcinomas did not differ in their alpha diversity from squamous cell carcinomas, although the content of Gram-positive bacteria increased significantly in the adenocarcinoma group (p = 0.0419). An analysis of an inflammatory infiltrate of tumor stroma showed a correlation of CD68, iNOS and FOXP3 with a histological type of tumor. For the first time we showed that high bacterial load in the tumor combined with increased iNOS expression is a favorable prognostic factor (HR = 0.1824; p = 0.0123), while high bacterial load combined with the increased number of FOXP3+ cells is a marker of poor prognosis (HR = 4.651; p = 0.0116). Thus, we established that bacterial load of the tumor has an opposite prognostic value depending on the status of local antitumor immunity.
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页数:17
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