Affiliation:
1. Baylor University
2. National Cancer Institute
3. National Institutes of Health
4. Harvard T.H. Chan School of Public Health, Harvard University
5. Resphera Biosciences, LLC
Abstract
Abstract
Esophageal carcinoma (ESCA) is a leading cause of cancer-related death worldwide, and Barrett’s esophagus (BE) is a strong risk factor along with smoking. Smoking is well-known to induce microbial dysbiosis and we asked if BE and esophageal microbiomes had shared microbial alterations that could provide novel biomarkers. We extracted DNA from BE tissues (n=5) and tumors of 158 patients in the NCI-MD case control study and sequenced the 16S rRNA gene (V3-4), with TCGA ESCA RNAseq (n = 173) and WGS (n = 139) non-human reads used as validation. We identified four taxa, Campylobacter, Prevotella, Streptococcus, and Fusobacterium as highly enriched in esophageal cancer across all cohorts. Using SparCC, we discovered that Fusobacteriumand Prevotella were also co-enriched across all cohorts. We then analyzed immune cell infiltration to determine if these dysbiotic taxa were associated with immune signatures. Using xCell to obtain predicted immune infiltrates, we identified a depletion of megakaryocyte-erythroid progenitor (MEP) cells in tumors with presence of any of the four taxa, along withenrichment of platelets in tumors with Campylobactor or Fusobacterium. Taken together, our results suggest that intratumoral presence of these co-occurring bacterial genera may confer tumor promoting immune alternations that allow disease progression in esophageal cancer.
Publisher
Research Square Platform LLC
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