Patient-matched tumours, plasma, and cell lines reveal tumour microenvironment- and cell culture-specific microRNAs

MicroRNAs (miRNAs) are small non-coding RNA molecules that are present in all cell types and bodily fluids and are commonly dysregulated in cancer. miRNAs in cancer have been studied by measuring levels in cell lines, tumour tissues, and in circulation; however, no study has specifically investigated miRNA expression in patient-matched samples across all three sample types. Canine osteosarcoma is a well-established spontaneously occurring model of human osteosarcoma for which matched samples are available. We analysed a panel of miRNAs by real-time quantitative PCR and compared across patients and sample types. While some miRNAs are highly expressed in all three sample types, tumour tissue and cell lines had the most in common. There were several miRNAs that were highly expressed in plasma and tumour tissue but not in cell lines and likely represent miRNAs produced in the tumour microenvironment. Two highly expressed miRNAs were exclusive to plasma and are known to be expressed in circulating cells. This study highlights the importance of considering sample type when studying miRNAs in cancer and demonstrates the power of using patient-matched samples.