ColoStem, a core oncofetal signature that identifies poor prognosis colorectal tumors

Abstract

Background: 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 oncofetal signature consisting of 28 upregulated and 8 downregulated genes that stratify patients with worse prognosis. Methods: We have generated and analyzed a metacohort which integrates 1118 samples from six colorectal cancer public datasets and performed qPCR analysis of paraffin-embedded and plasma samples from our in-house cohort of colorectal cancer tumors. Results: We uncovered a core oncofetal signature, which we have called ColoStem, composed of 5 genes upregulated and 3 genes downregulated that displays prognosis value in a multivariate analysis. We also defined EpiColoStem, a reduction of ColoStem, as a pure 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 prognosis of CRC patients with a simple an affordable method. Initial analysis of plasma samples indicated that both signatures could be adapted for its use in liquid biopsy. Conclusions: Our results reveal ColoStem and EpiColoStem tests as valuable tools for refining patient prognosis through the identification of fetal-type CRC tumors.