Expression of miRNAs in patient-derived cancer models and models of drug resistance

We examined whether tumor samples can be stratified according to miRNA expression profiles. Overall design: We performed miRNA sequencing in 12 patient derived cancer models (PDCMs, organoids/spheroids) and models of drug resistance. These included the melanoma WM1366 cell line and both related BRAF/MEK inhibitor resistant daughter cell lines WM1366VCi and WM1366DTi. In addition, we included 8 patient-derived 3D cancer models, represented by two spheroid models (CRC02-SP, CRC03-SP) and three organoid models (CRC01-OG, CRC03-OG, CRC04-OG) from patients with CRC. In addition, we studied one organoid model from a patient with cancer of unknown primary (CUP01-OG), and one spheroid culture from a patient with teratoma (TER01-SP). To also test whether and how miRNA expression differs between related samples, we included a normal colon mucosa organoid culture (CRC01NM-OG) for the CRC patient 1 (CRC01-OG). In addition, we created an irinotecan resistant subclone of the CRC patient 2 spheroid culture (CRC02-SP) by constantly adding increasing concentrations of SN38 for at least 4 passages.