RNAseq analysis on metastatic Colorectal Cancer. RNAseq analysis on metastatic Colorectal Cancer

In this study we want present a bank of metastatic colorectal cancer (mCRC) Patient Derived Organoids (PDOs) obtained from Patient Derived Xenografts (PDXs). These models are annotated with different omics to advance our understanding of CRC. We wanted to create a resource for the scientific community to assess the predictive reliability of these preclinical models. We performed comparative analyses between PDOs and matched PDXs to assess the similarities of these two platforms regarding molecular profiles and transcriptional classification. Moreover, we analyzed how these models respond to Cetuximab, a chimeric monoclonal antibody, normally given to patients after chemotherapy, that inhibits EGFR. After having assessed models’ reliability with Cetuximab, we aimed at identifying potential synergistic drugs to individuate new possible therapeutic prospects. Overall design: Transcriptional profiles were obtained with RNA sequencing – we aligned reads with STAR on a hybrid human-mouse genome, in order to remove the mouse derived reads without requiring a pre-filtering step. Reads were assigned to human genes with FeatureCounts, then we used DESeq2 to obtain normalized expression values and perform differential expression analyses. All analytical pipelines have been implemented with Snakemake as a workflow management system, to ensure portability and reproducibility. ---------------------------------------------- Authors state the following "Raw data with reads from our samples need controlled access, since they derive from human tumors." ---------------------------------------------- Clarification for columns “cell type”, “cell line” and “treatment”. The column “cell type” defines the type of samples LM: liver metastasis PR: primary (from colon) The column “cell line” defines the origin of samples H: patients X: xenografts O: organoids The column “treatment” describes the experiments done with cetuximab cetuxi: treated samples (72h (written as h) or 6w for xenografts) NT: non-treated control The word “basale” indicates xenografts or organoids grown in normal conditions. They are not the non-treated control of the cetuximab experiments.