The characteristic of epithelial-specific phenotypes and immunosuppressive microenvironment in the context of tumour budding in colorectal cancer
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Background
A small cluster of up to four cells, defined as tumour budding (TB), has been well studied as an independent promising prognostic marker in CRC. However, its underlying mechanism in CRC is unclear.
Methods
Multi-omic approaches from bulk RNA as well as regional GeoMx bulk RNA were used to identify the underlying mechanism of TB and its possible correlation with tumour microenvironment in CRC tissue. The results were validated using immunohistochemistry (IHC) and multiplex immunofluorescence (mIF) staining.
Results
Patients with high TB have a worse outcome and associated with adverse clinical factors. Bulk RNA expression revealed that tumours with high TB are significantly enriched for gene signatures related to epithelial-mesenchymal transition (EMT), TNF-α and TGF-β, in both independent CRC cohorts. Additionally, regional bulk RNA expression from non-tumour (PanCK-) invasive areas showed that tumours with high TB were significantly associated with a decreased immune activity. Multiplex immunofluorescence (mIF) suggested a close proximity of regulatory T cells and pan-macrophages to individual buds.
Discussion
This study confirms the prognostic role of TB in CRC in two independent CRC cohorts and gives an insight into its underlying mechanism and potential interactions with the tumour microenvironment in CRC.
