Effects of green tea on miRNA and microbiome of oral epithelium.

Consumption of green tea (GT) extracts or purified catechins has shown the ability to prevent oral and other cancers and inhibit cancer progression in rodent models, but the evidence for this in humans is mixed. Working with humans, we sought to understand the source of variable responses to GT by examining its effects on oral epithelium. Lingual epithelial RNA and lingual and gingival microbiota were measured before and after 4 weeks of exposure in tobacco smokers, whom are at high risk of oral cancer. GT consumption had on average inconsistent effects on miRNA expression in the oral epithelium. Only analysis that examined paired miRNAs, showing changed and coordinated expression with GT exposure, provided evidence for a GT effect on miRNAs, identifying miRNAs co-expressed with two hubs, miR-181a-5p and 301a-3p. An examination of the microbiome on cancer prone lingual mucosa, in contrast, showed clear shifts in the relative abundance of Streptococcus and Staphylococcus, and other genera after GT exposure. These data support the idea that tea consumption can consistently change oral bacteria in humans, which may affect carcinogenesis, but argue that GT effects on oral epithelial miRNA expression in humans vary between individuals.

Improving accuracy of RNA-based diagnosis and prognosis of oral cancer by using noninvasive methods.

RNA-based diagnosis and prognosis of squamous cell carcinoma has been slow to come to the clinic. Improvements in RNA measurement, statistical evaluation, and sample preservation, along with increased sample numbers, have not made these methods reproducible enough to be used clinically. We propose that, in the case of squamous cell carcinoma of the oral cavity, a chief source of variability is sample dissection, which leads to variable amounts of stroma mixed in with tumor epithelium. This heterogeneity of the samples, which requires great care to avoid, makes it difficult to see changes in RNA levels specific to tumor cells. An evaluation of the data suggests that, paradoxically, brush biopsy samples of oral lesions may provide a more reproducible method than surgical acquisition of samples for miRNA measurement. The evidence also indicates that body fluid samples can show similar changes in miRNAs with oral squamous cell carcinoma (OSCC) as those seen in tumor brush biopsy samples - suggesting much of the miRNA in these samples is coming from the same source: tumor epithelium. We conclude that brush biopsy or body fluid samples may be superior to surgical samples in allowing miRNA-based diagnosis and prognosis of OSCC in that they feature a rapid method to obtain homogeneous tumor cells and/or RNA.