Metastasis and Cancer Stem Cell Markers Identify Two Colorectal Cancer Subtypes with Different Molecular and Clinical Features

Colorectal cancer (CRC) is among the top prevalent cancer types with lethal outcome in the United States and worldwide. CRC inter-tumor heterogeneity highlights the importance of identifying molecular markers for meaningful classification and prognosis. The recently published Consensus Molecular Subtypes (CMS) represent a widely used molecular subtyping system of CRC. However, our analyses indicate that clear heterogeneity still exists in some CMSs. In this work, we demonstrate that both CMS2 and CMS4 are composed of two molecularly distinct subtypes. We named them S1 and S2, short for subtype 1 and subtype 2. Our results indicate that the two subtypes also differ clinically. Notably, S2 exhibits more frequent lymphatic invasion across CRCs and more frequent metastasis events within CMS2 patients.