Relationship between tumor microbiota transcriptional activity and gene expression in breast cancer.

BACKGROUND: A few studies have reported the distribution of the microbiota in breast cancer tissues, but few reports have compared the microbiota in different subtypes of breast cancer tissue. Moreover, no study has reported on the relationship between the microbiota and gene expression in breast tumor. METHODS: Sections of formalin-fixed paraffin-embedded (FFPE) tissue were prepared from the breast tumors of 70 patients and were subjected to microarray analysis to identify gene expression profiles. The same total RNA samples were also used to analyze the microbiota activity in tumor tissues by performing 16 S rRNA sequencing and internal transcribed spacer (ITS) sequencing of reverse transcript cDNA with Illumina Miseq. Pearson's correlation coefficient was used for calculating the correlation between microbial relative activity and gene expression. RESULTS: The microbiota transcriptional activity of 70 FFPE samples mainly consisted of the phyla Bacteroidetes, Firmicutes and Proteobacteria. Prevotella_9, Bacteroides and Alloprevotella were the most active genera in ER+/HER2-, ER+/HER2 + and ER-/HER2 + tumors, while triple-negative samples exhibited a higher activity of Lactobacillus. In ER-negative samples (triple-negative and ER-/HER2+), 479 genes, including the breast carcinogenesis genes phospholipase A2, histone cluster 2, Crk-like, and cyclin D1, were significantly positive associated with the activity of Lactobacillus. CONCLUSION: This was the first study to clarify an association between the breast tumor microbiota transcriptional activity and the expression of carcinogenesis genes in ER-negative breast cancer. Changes in the microbiota of breast tissue induced by external factors might be one of the key causes of ER negative breast cancer.

The Wnt gatekeeper SFRP4 modulates EMT, cell migration and downstream Wnt signalling in serous ovarian cancer cells.

Aberrant Wnt signalling is implicated in numerous human cancers, and understanding the effects of modulation of pathway members may lead to the development of novel therapeutics. Expression of secreted frizzled related protein 4 (SFRP4), an extracellular modulator of the Wnt signalling pathway, is progressively lost in more aggressive ovarian cancer phenotypes. Here we show that recombinant SFRP4 (rSFRP4) treatment of a serous ovarian cancer cell line results in inhibition of ß-catenin dependent Wnt signalling as measured by TOP/FOP Wnt reporter assay and decreased transcription of Wnt target genes, Axin2, CyclinD1 and Myc. In addition, rSFRP4 treatment significantly increased the ability of ovarian cancer cells to adhere to collagen and fibronectin, and decreased their ability to migrate across an inflicted wound. We conclude that these changes in cell behaviour may be mediated via mesenchymal to epithelial transition (MET), as rSFRP4 treatment also resulted in increased expression of the epithelial marker E-cadherin, and reduced expression of Vimentin and Twist. Combined, these results indicate that modulation of a single upstream gatekeeper of Wnt signalling can have effects on downstream Wnt signalling and ovarian cancer cell behaviour, as mediated through epithelial to mesenchymal plasticity (EMP). This raises the possibility that SFRP4 may be used both diagnostically and therapeutically in epithelial ovarian cancer.