ColoStem, a core transcriptional signature that identifies poor prognosis fetal-type colorectal tumors
We have previously shown that non-curative chemotherapy imposes fetal conversion and high metastatic capacity to cancer cells. Analysis of public colorectal cancer datasets confirms the existence of a fetal signature consisting of 28 upregulated and 8 downregulated genes that stratify patients with worse prognosis. We have analyzed a metacohort generated by the integration of several colorectal cancer datasets and performed qPCR analysis of paraffin-embedded and plasma samples from our in-house cohort of colorectal cancer tumors. We uncovered a core fetal signature, which we have called ColoStem, composed of 5 genes upregulated and 3 genes downregulated that display prognosis value in a multivariate analysis. We also define EpiColostem as a purer epithelial signature with comparable prognosis value as ColoStem. By qPCR analysis of RNA extracted from paraffin-embedded tissues, we demonstrated the actual possibility of using ColoStem and EpiColoStem to refine the prognostication of CRC patients with a simple an affordable method. Initial analysis of plasma samples indicates that both signatures could be adapted for its use in liquid biopsy. Our results reveal ColoStem and EpiColoStem tests as valuable tools for the identification of fetal-type CRC tumors thus refining patient prognosis. Overall design: We analyzed bulk RNAseq samples obtained from colorectal cancer Patient-Derived Organoids: 3xnon-fetal (PDO4, PDO10 and PDO66) and 3xfetal (PDO5, PDO27 and PDO127B), plus 2xtreated with 5-FU+Irinotecan (PDO66), each in triplicates.