Integrative multi-omics of matched primary and liver metastatic colorectal cancer organoids identifies putative molecular targets

Hepatic metastasis from colorectal cancer (CRC) mainly accounts for the dismal prognosis of advanced CRC. Metastasized tumor cells exhibit strong resistance to commonly used systemic chemotherapy, which causes the high mortality of colorectal liver metastasis (CLM) patients. Although previous studies using biological resources have suggested multiple metastatic factors, molecular integration into chemotherapeutic responses is seldom studied. In this study, we established five pairs of CLM organoids, which were subjected to a multi-omics approach including genetic, transcriptional, exosomal miRNA and pharmacological analyses. These multi-omics layers were interlinked through machine learning analysis to construct a drug response prediction model. Our approach not only recapitulated druggable molecular targets that were specifically dysregulated in LM organoids but also potentially revealed a statistical connection to systemic therapy regimens.