Fusobacterium nucleatum-Mediated Alteration in Expression of VEGFand CCL3 Genes and KRAS Mutation in Colorectal Cancer Patients

Background: Colorectal cancer (CRC) is the third most common cancer worldwide, and its development is influenced by genetic and environmental factors, including the gut microbiota. Recent studies have reported an association between Fusobacterium nucleatumabundance and CRC. Objectives: This study aimed to investigate the abundance of F. nucleatumin CRC and polyp patients and its association with the expression of chemokine ligand -3( CCL3), vascular endothelial growth factor ( VEGF), and nuclear factor-kappa B ( NF-KB11) genes and the presence of deoxyribonucleic acid (DNA) mutations and polymorphisms in the Kirsten rat sarcoma viral oncogene homolog ( KRAS) gene. Methods: A total of 80 biopsy samples were collected from CRC, polyp, and colitis patients. Moreover, F. nucleatumabundance was measured by quantitative polymerase chain reaction (qPCR). The expression of CCL3, VEGF, and NF-KB11genes was measured by reverse transcription polymerase chain reaction (RT-PCR). Additionally, KRASgene mutations and polymorphisms were detected by the Mutation Surveyor software (V5.1.2). Results: The results showed that F. nucleatumabundance was significantly higher in CRC and polyp patients than in colitis patients (P 0.05). The expression of CCL3and VEGFgenes was also significantly higher in F. nucleatum-positive samples (P 0.05). However, NF-KB11gene expression was non-significant. Fusobacterium nucleatum-positive biopsy samples had a higher frequency of KRASgene mutations and polymorphisms than F. nucleatum-negative CRC patients (odds ratio = 3). Most of the mutations observed in the positive samples were (6144A AT,31E E) at exon 2 of the KRASgene. Conclusions: The study findings suggest that F. nucleatummight play a role in CRC and polyp development and contribute to KRASgene mutations. Therefore, targeting F. nucleatumin the gut microbiota could be a potential therapeutic strategy for preventing CRC and polyp development.