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.
Highlights
Numerous histological subtypes in colorectal cancer (CRC) are defined by mucin-related phenotypes
In this study, it is demonstrated that consensus molecular subtype 3 (CMS3) subtype TCGA COAD exhibits elevated expression of goblet cell markers, which is an effective surrogate for goblet cell content
CMS3 subtype tumors represent a distinct subtype from COAD tumors classified as mucinous adenocarcinomas, which were only associated with high expression of MUC2
Summary
Numerous histological subtypes in colorectal cancer (CRC) are defined by mucin-related phenotypes. It is understood that these pathologies arise due to aberrant processes related to the secretion of mucin. It is unclear how well these pathological classifications track with goblet cell content, or in other words, the proportion of goblet cells in a tumor. As a result, it is unclear whether goblet cell content is associated with mucin-related histological subtypes, even though this may be an important consideration in explaining the heterogeneity of outcomes in patients with mucinous CRC [2]. There are no effective methods in place to rapidly query goblet cell content across many tumor samples
Sign-in/Register to view highlights & summary 
Submitted Version (
Free)
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call