Co-enrichment of cancer-associated bacterial taxa is correlated with immune cell infiltrates in esophageal tumor tissue.

Esophageal carcinoma (ESCA) is a leading cause of cancer-related death worldwide, and certain oral and intestinal pathogens have been associated with cancer development and progression. We asked if esophageal microbiomes had shared alterations that could provide novel biomarkers for ESCA risk. We extracted DNA from tumor and non-tumor tissue of 212 patients in the NCI-MD case control study and sequenced the 16S rRNA gene (V3-4), with TCGA ESCA RNA-seq (n = 172) and WGS (n = 123) 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 Fusobacterium and 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 with enrichment 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 alterations that allow disease progression in esophageal cancer.

Identification of uterine leiomyoma genes developmentally reprogrammed by neonatal exposure to diethylstilbestrol.

Environmental exposures during development can alter susceptibility later in life to adult diseases including uterine leiomyoma, a phenomenon termed developmental reprogramming. The goal of this study was to identify genes developmentally reprogrammed by diethylstilbestrol (DES) and aberrantly expressed in leiomyomas. Transcriptional profiling identified 171 genes differentially expressed in leiomyomas relative to normal myometrium, of which 6/18 genes with putative estrogen responsive elements and confirmed to be estrogen-responsive in neonatal uteri were reprogrammed by neonatal DES exposure. Calbindin D9k and Dio2, normally induced by estrogen, exhibited elevated expression in DES-exposed animals during both phases of the estrus cycle. Gdf10, Car8, Gria2, and Mmp3, genes normally repressed by estrogen, exhibited elevated expression in DES-exposed animals during the proliferative phase, when estrogen is highest. These data demonstrate that neonatal DES exposure causes reprogramming of estrogen-responsive genes expressed in uterine leiomyomas, leading to over-expression of these genes in the myometrium of exposed animals prior to the onset of tumorigenesis.