CIN-associated proteins and molecular mechanisms in colorectal cancer

Chromosomal instability (CIN) involves about 70% of colorectal cancers (CRCs). It is associated with poor prognosis and drug resistance. From a clinical perspective, it is essential to characterize this type of tumors to effectively guide therapeutic strategies. In this study we studied the CIN profile of our patient derived organoids (PDOs) in terms of genome, transcriptome and proteome. By applying Weighted Genome Instability Index (wGII) to identify it, we showed a good correlation between organoids and tissues. In addition, organoids recapitulated transcriptomic CIN features. Moreover, our PDOs allowed us to explore how CIN shapes the transcriptome and proteome and to uncover significant relation between metabolic rewiring and epithelial-mesenchymal transition in CIN CRC PDOs. Our results shed light on some CIN-associated proteins and molecular mechanisms putatively required to cope with the burden on cellular fitness imposed by this context.