Abstract
Mounting evidence suggests that changes in microbiome are linked to development of cancer and its aggressiveness. Microbiome profiles in human breast tissue previously presumed to be sterile, have recently been characterized using high-throughput technologies. Recent findings of microbiome variation between benign and malignant disease provides a rationale for exploring microbiomes associated with cancer during tumor progression. We assessed microbiomes of aseptically collected human breast tissue samples in this study, using needle biopsy from patients with benign and malignant tumors of different histological grading, using 16S rRNA gene amplicon sequencing. This is consistent with previous studies, and our results identified distinct microbiome profiles in breast tissues from women with cancer as compared to women with benign breast disease in Chinese cohorts. The enriched microbial biomarkers in malignant tissue included genus Propionicimonas and families Micrococcaceae, Caulobacteraceae, Rhodobacteraceae, Nocardioidaceae, Methylobacteriaceae, which appeared to be ethno-specific. Further, we compared microbiome profiles in malignant tissues of three different histological grades. The relative abundance of family Bacteroidaceae decreased and that of genus Agrococcus increased with the development of malignancy. KEGG pathways inferred by PICRUSt showed that biotin and glycerophospholipid metabolism had significant differences in all three grades. Glycerophospholipid and ribosome biogenesis increased in grade III tissue as compared to grades I and II. Flavonoid biosynthesis significantly decreased in grade III tissue. The specific correlation of these potential microbial biomarkers and indicated pathways with advanced disease could have broad implications in the diagnosis and staging of breast cancer. Further large-cohort investigation of the breast cancer microbiome and its potential mechanism in breast cancer development are essential.
Highlights
The recent appreciation of the influence of microbiota on human health and disease sheds light on whether microbes play a role in cancer development and progression [1]
We compared the microbiome profiles in 22 benign and 72 malignant breast cancer patients (Table 1)
Genus Propionicimonas and five families Micrococcaceae, Caulobacteraceae, Rhodobacteraceae, Nocardioidaceae and Methylobacteriaceae were abundant in malignant disease compared to benign disease, and only two genera were enriched in benign disease state (LDA>2)
Summary
The recent appreciation of the influence of microbiota on human health and disease sheds light on whether microbes play a role in cancer development and progression [1]. The differences in the microbiome of human breast tissue from women with benign and malignant disease provided insights for subsequent investigations on the role of the breast microbiome in breast carcinogenesis and breast cancer prevention [15]. We characterized and compared the microbiome of aseptically collected human breast samples from patients with benign and malignant cancer having different histological grades using needle biopsy and 16S rRNA gene amplicon sequencing. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to infer KEGG pathways in microbiomes of benign and different malignant tumors
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