Heterogeneity of tumor microenvironment cell groups in inflammatory and adenomatous polyposis coli mutant colorectal cancer based on single cell sequencing.

Abstract

Background: The prognosis of colorectal cancer (CRC) is known to vary across different etiologies. Inflammatory bowel disease (IBD) is often identified as a factor contributing to poorer outcomes. However, the mechanisms that link IBD to a worse CRC prognosis remain to be elucidated. We aim to reveal the complex tumor microenvironment of inflammatory CRC and provide a weak theoretical basis for the treatment of different subtypes of CRC.

Methods: We conducted a bioinformatics analysis using single-cell RNA sequencing (scRNA-seq) data from 8,494 individual CRC cells derived from azoxymethane (AOM)/dextran sodium sulfate (DSS) and adenomatous polyposis coli (APC) mutant datasets. The expression of implicated genes in both tumor and adjacent normal tissues was examined via immunohistochemistry and immunofluorescence.

Results: CRC from AOM/DSS treatment contained fewer immune cells relative to APC-mutant CRC. However, a macrophage subcluster enriched for inflammatory factors was more prevalent in AOM/DSS datasets. This subcluster exhibited elevated expression of APOE and BNIP3. Immunofluorescence and immunohistochemistry of patient samples confirmed that the expression of APOE and BNIP3 was higher in adjacent normal tissues compared to tumors.

Conclusions: Our findings shed light on the heterogeneous microenvironments in IBD and APC-mutant CRC. Furthermore, we identify APOE as a potential biomarker for CRC recurrence.