Decrease in natural killer cell associated gene expression as a major characteristic of the immune status in the bloodstream of colorectal cancer patients

Abstract

Early detection and stratification of patients with colorectal cancer (CRC) are major challenges, particularly in the context of the development of new therapies. Several screening strategies are already in place in various countries, but compliance remains a major issue, mainly due to logistics or discomfort for the patients. In this study, we hypothesized that transcriptional signatures associated with leukocytes in peripheral blood can be informative to the identification of CRC patients. Gene expression was studied using RNA extracted from whole blood samples collected in PAXgene tubes and DNA microarrays. Analyzing 119 CRC patients and 101 colonoscopy-negative control (CNC) samples, we observed 327 differentially expressed genes (DEG), mostly associated with immune cell activation and trafficking. Natural Killer (NK) cell signaling and cytotoxicity associated genes appeared to undergo major changes in CRC peripheral blood samples. These changes were more pronounced in the advanced stages of the disease. A summarizing score of the expression of 10 genes related to NK cells interestingly revealed a marked heterogeneity within the CRC Stage IV group, suggesting possible further stratification of the patients. This study shows the potential of transcriptomics in peripheral blood to discover biomarkers and provides new insight on the immune response in colorectal cancer. In addition to preparing a possible alternative to current screening modalities, these results also show that the expression analysis of genes like those related to NK cells should allow the stratification of patients with colorectal cancer, opening the door to personalized medicine.