Associations of mucinous differentiation and mucin expression with immune cell infiltration and prognosis in colorectal adenocarcinoma

Abstract

The production of extracellular mucus and expression of mucins are commonly aberrant in colorectal cancer, yet their roles in tumour progression remain unclear. To investigate the potential influence of mucus on immune response and prognosis, we analysed mucinous differentiation (non-mucinous, 0%; mucinous component, 1–50%; mucinous, >50%) and its associations with immune cell densities (determined with three multiplex immunohistochemistry assays or conventional immunohistochemistry) and survival in 1049 colorectal cancer patients and a validation cohort of 771 patients. We also assessed expression patterns of transmembrane (MUC1, MUC4) and secreted (MUC2, MUC5AC and MUC6) mucins using immunohistochemistry. Mucinous differentiation was associated with higher densities of CD14+HLADR– immature monocytic cells and M2-like macrophages in mismatch repair (MMR) proficient tumours, and lower T-cell densities in MMR-deficient tumours. Mucinous differentiation was not associated with cancer-specific survival in multivariable Cox regression models. Higher cytoplasmic MUC1 expression independently predicted worse cancer-specific survival (multivariable HR for high vs. negative to low expression, 2.14; 95% CI: 1.26–3.64). It was also associated with increased myeloid cell infiltration in MMR-proficient tumours. Although mucinous differentiation did not independently predict survival, extracellular mucus and MUC1 expression could promote tumour progression through immunosuppression.