The relationship between KRAS gene mutation and intestinal flora in tumor tissues of colorectal cancer patients

Colorectal Cancer

Ann Transl Med. 2020 Sep;8(17):1085. doi: 10.21037/atm-20-5622.


BACKGROUND: Colorectal cancer is among the most prominent malignant tumors endangering human health, with affected populations exhibiting an increasingly younger trend. The Kirsten ras (KRAS) gene acts as a crucial regulator in this disease and influences multiple signaling pathways. In the present study, the KRAS gene mutation-induced alteration of intestinal flora in colorectal cancer patients was explored, and the intestinal microbes that may be affected by the KRAS gene were examined to provide new insights into the diagnosis and treatment of colorectal cancer.

METHODS: Deoxyribonucleic acid (DNA) was extracted from 177 colorectal cancer patients in our hospital. The mutation of the KRAS gene was subsequently detected using real-time fluorescence quantitative polymerase chain reaction (qPCR), and survival analysis was performed. Moreover, genomic DNA was extracted from the fecal microbes in 30 of these patients, and the differences in the intestinal flora between mutation and non-mutation groups were evaluated using linear discriminant analysis (LDA) Effect size (LEfSe) analysis.

RESULTS: KRAS gene mutation substantially affected the distant metastasis of colorectal cancer, and the survival prognosis in the non-mutation group was significantly superior compared to the mutation group. The mutation group had a notably higher prevalence of microbes including Roseburia, Parabacteroides, Metascardovia, Staphylococcus, Staphylococcaceae, and Bacillales than the non-mutation group. The presence of microbes in the non-mutation group, such as Clostridiales, Bacteroidetes, Lachnospiraceae, Coprococcus, and Ruminococcaceae was markedly higher than in the mutation group. Firmicutes were negatively correlated with the presence of Actinomyces and Bacteroidetes, while Bacteroidetes were positively associated with the level of Actinomyces.

CONCLUSIONS: In colorectal cancer, KRAS gene mutation can remarkably affect the survival prognosis and change the composition and abundance of intestinal flora, such as Roseburia, Parabacteroides, Metascardovia, Staphylococcus, and Bacillales, thereby influencing tumor development.