Consensus molecular subtyping of colorectal cancers is influenced by goblet cell content

Abstract A critical obstacle in the field of colorectal cancer (CRC) is the establishment of precise tumor subtypes to facilitate the development of targeted therapeutic regimens. While dysregulated mucin production is a histopathological feature of multiple CRC subtypes, it is not clear how well these pathologies are associated with the proportion of goblet cells in the tumor, or whether or not this proportion is variable across all CRC. This study demonstrates that consensus molecular subtype 3 (CMS3) CRC tumors and cell lines are enriched for the expression of goblet cell marker genes. Further, the proportion of goblet cells in the tumor is associated with the probability of CMS3 subtype assignment and these CMS3 subtype tumors are mutually exclusive from mucinous adenocarcinoma pathologies. This study provides proof of principle for the use of machine learning classification systems to subtype tumors based on cellular content, and provides further context regarding the features weighing CMS3 subtype assignment.