Prognostic Significance of the Microbiome and Stromal Cells Phenotype in Esophagus Squamous Cell Carcinoma

Abstract

Esophageal cancer is one of the most aggressive malignant neoplasms, with low survival rates and limited treatment options. In this study we analyzed the microbiome composition and the phenotype of inflammatory tumor infiltrate in squamous cell carcinoma of esophagus (ESCC) and examined possible relationships between them and their prognostic significance. We found that the predominant phyla of microorganisms found in both tumors and adjacent normal tissues were Firmicutes, Proteobacteria, Actinobacteria, Gemmatimonadetes and Bacteroidetes. We established that only bacteria of the genus Staphylococcus differ between tumors and normal tissues. We found a significant correlation between bacterial burden and the phenotype of the tumor stroma. Namely, a group of tumors characterized by a high expression of CD206 (r = −0.3976, p = 0.0056) in the stroma and iNOS (r = −0.2953, p = 0.0439) in tumor cells is characterized by a higher bacterial burden. Further, we established that in the group with a high content of CD206+ macrophages, there is also a predominance of gram-positive bacteria over gram-negative ones. We found that gram-positive bacterial burden is associated with disease prognosis in ESCC showing high content of CD206+ macrophages. In conclusion we established that the tumor microbiome, can be prognostically significant for ESCC when combined with other stromal markers.

Comprehensive Analysis of Stromal and Serum Markers in Gastric Cancer

“…The literature suggests that CD163 expression is often associated with an unfavorable prognosis of various solid tumors [ 16 ]. However, for gastrointestinal tumors, it has been shown that CD163 can be a marker of good prognosis, particularly in esophageal cancer [ 17 ] and colorectal cancer [ 18 ]. For GC, an increased density of CD163+ macrophages in tumor stroma has been shown to be associated with the activation of the immune response and improved patient survival according to single-factor analysis [ 19 ].…”

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

“…Previously, we have shown that in the case of lung and esophageal cancer, a high bacterial load in the tumor, combined with increased expression of iNOS, is a favorable prognostic factor, and a high bacterial load, combined with local immunosuppression, on the contrary, is a marker of poor prognosis [ 23 , 24 ]. Here, we demonstrate that for kidney cancer, iNOS is an independent marker of a favorable prognosis.…”

“…The samples were divided into two groups depending on the presence of iNOS-positive cells in the stroma. Tumor staining was classified as positive when clear cytoplasmic staining was present in ≥1% of tumor cells for iNOS [ 24 ].…”

“…For the purposes of analysis, the metric was the number of cycles to cross the threshold (Ct value) as a measure of 16s rRNA gene load and hence bacterial burden. A higher bacterial load resulted in a lower number of cycles to cross the threshold—that is, a lower Ct value [ 24 , 25 ].…”

Состав И Фенотип Опухолевой Стромы Как Маркер Прогноза Заболевания

“…Одной из таких перспективных комбинаций может являться комплексная морфологическая оценка стромы в совокупности и бактериальной нагрузкой. Использование комплексного анализа клеточного и бактериального состава в опухоли предложено относительно недавно [53,54], однако набирает популярность [55][56][57] Дальнейшие исследования показали, что что повышенное содержание бактерий наблюдается в группах опухолей НМРЛ с высокой экспрессией iNOS в опухолевых клетках и высоким содержанием FoxP3+ стромальных Т-клеток. В целом добавление оценки общей бактериальной нагрузки в опухоли кардинально меняет картину выживаемости пациентов.…”