Association of SIGLEC9 Expression with Cytokine Expression, Tumor Grading, KRAS, NRAS, BRAF, PIK3CA, AKT Gene Mutations, and MSI Status in Colorectal Cancer

Curr Issues Mol Biol. 2024 Nov 29;46(12):13617-13646. doi: 10.3390/cimb46120814.

Abstract

SIGLEC9 (sialic acid-binding Ig-like lectin 9) is a molecule thought to have a significant influence on the immune properties of the colorectal cancer (CRC) tumor microenvironment (TME). In our study, we assessed the expression of the SIGLEC9 protein in CRC tissue and the surgical margin tissue. Using RT-PCR, we analyzed mutations in the KRAS, NRAS, BRAF, PIK3CA, and AKT genes. We observed a significantly elevated expression of the SIGLEC9 protein in CRC tissue compared to the control group. No significant differences were observed in SIGLEC9 protein expression depending on mutations in the KRAS, NRAS, BRAF, PIK3CA, and AKT genes or microsatellite instability (MSI) status. However, we found a significantly higher expression of the SIGLEC9 protein in high-grade tumors compared to the low-grade tumors group. SIGLEC9 expression was significantly associated with the expression of multiple cytokines, chemokines, and growth factors in the CRC TME. These associations suggest the significant potential of SIGLEC9 as a molecule that plays a crucial role in shaping the immune properties of the CRC TME, as well as its potential therapeutic relevance, particularly in the group of high-grade CRC tumors.

Keywords: K-ras oncogene; colorectal cancer (CRC); human sialic-acid-binding immunoglobulin-like lectin-9 (SIGLEC9); instability; microenvironment; microsatellite; proto-oncogene proteins B-raf (BRAF); tumor.

Grants and funding

This project was supported by the statutory funds of the Medical University of Silesia, Katowice, Poland. This research was funded by the Ministry of Education and Science, Poland, grant number SKN/SP/570127/2023.