Key findings from the study include:
- Nearly 80 CRC-derived cell lines are classified into five categories based on the levels of MUC2 (the main mucous product of goblet cells) and TFF3 (an associated gene product).
- Identification of five distinct patterns of MUC2 and TFF3 expression, which can be easily identified in tumour specimens, allowing for a finer characterisation of CRCs concerning goblet cell differentiation.
- It was discovered that approximately 30% of all CRCs express TFF3 but not MUC2, a previously unrecognised subgroup.
- Identification of up to 12 genes (including MUC2, TFF3, ATOH1, SPDEF, CDX1, CDX2, GATA6, HES1, ETS2, OLFM4, TOX3, and LGR5) that may be involved in selection against goblet cell differentiation in CRC through changes in methylation rather than mutations.
- Highlighting the role of LGR5 in controlling differentiation rather than direct control of cell growth, challenging previous assumptions.
Sir Walter Bodmer, the study's lead author, stated, “Our findings emphasise the importance of methylation changes in driving cancer progression. This finer characterisation of CRCs for goblet cell differentiation could pave the way for more targeted and effective treatments.”
The study’s results provide valuable insights into the factors driving cancer progression and underscore the potential for improved diagnostic and therapeutic strategies for colorectal cancer, particularly in identifying and targeting specific subgroups based on goblet cell differentiation.