ColoStem, a core oncofetal signature that identifies poor prognosis colorectal tumors
摘要
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.
MethodsWe 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.
ResultsWe 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.
ConclusionsOur results reveal ColoStem and EpiColoStem tests as valuable tools for refining patient prognosis through the identification of fetal-type CRC tumors.