The clinical and immune features of CD14 in colorectal cancer identified via large-scale analysis.

Background: Cancer immunotherapies have achieved great progress in colorectal cancer (CRC). However, only a small subset of CRC patients with microsatellite instability (MSI) can obtain benefits from immune checkpoint inhibitors (ICIs). Nearly 85% of all CRC patients have microsatellite-stable (MSS) disease, which does not respond to ICIs. Increasing evidence has revealed that CD14 promotes tumor growth and induces an immunosuppressive environment through CD14 immunosuppressive cells. However, a systematic exploration of CD14 in CRC is lacking.

Method: A total of 644 samples with transcriptome data and 566 samples with microarray data were investigated in this study, including TCGA RNA-Seq and GSE39582 microarray. R software was the main tool for graphical work and statistical analysis.

Results: CD14 was upregulated in the MSI-H, BRAF-mutant, right-sided disease, and hypermethylation groups. Cases with high CD14 expression were related to the CMS4 subtype and had frequent mutation of driver oncogenes. CD14 expression was associated with the regulation of immune system processes in gene ontology analysis. The cytokine-cytokine receptor interaction was associated with CD14 expression. Moreover, CD14 was associated with high immune and stromal infiltration, and CD14 synergized with immune checkpoints. Additionally, CD14 was involved in immune and inflammatory responses. Finally, high CD14 expression predicted worse outcomes and was an independent negative indicator of prognosis in CRC, which was further confirmed in tissue microarray.

Conclusion: Our findings indicated that CD14 expression was associated with specific clinical characteristics. High CD14 expression might represent pre-existing immunity and have a high correlation with immune checkpoints. Moreover, CD14 correlated with poor clinical outcomes in CRC. Therefore, the CD14 molecule promises to be a potential target to enhance the immunotherapy of colorectal cancers.