Pks-positive Escherichia coli in tumor tissue and surrounding normal mucosal tissue of colorectal cancer patients

Abstract

A significant association exists between the gut microbiome and colorectal carcinogenesis, as well as cancer progression. It has been reported that Escherichia coli (E. coli) containing polyketide synthetase (pks) island contribute to colorectal carcinogenesis by producing colibactin, a polyketide-peptide genotoxin. However, the functions of pks⁺ E. coli in initiation, proliferation, and metastasis of colorectal cancer (CRC) remain unclear. We investigated the clinical significance of pks⁺ E. coli to clarify its functions in CRC. This study included 413 patients with CRC. Pks⁺ E. coli of tumor tissue and normal mucosal tissue were quantified using droplet digital PCR. Pks⁺ E. coli was more abundant in Stages 0-I tumor tissue than in normal mucosal tissue or in Stages II-IV tumor tissue. High abundance of pks⁺ E. coli in tumor tissue was significantly associated with shallower tumor depth (hazard ratio [HR] = 5.0, 95% confidence interval [CI] = 2.3-11.3, p < 0.001) and absence of lymph node metastasis (HR = 3.0, 95% CI = 1.8-5.1, p < 0.001) in multivariable logistic analyses. Pks⁺ E. coli-low and -negative groups were significantly associated with shorter CRC-specific survival (HR = 6.4, 95% CI = 1.7-25.6, p = 0.005) and shorter relapse-free survival (HR = 3.1, 95% CI = 1.3-7.3, p = 0.01) compared to the pks⁺ E. coli-high group. Pks⁺ E. coli was abundant in Stages 0-I CRC and associated with CRC prognosis. These results suggest that pks⁺ E. coli might contribute to carcinogenesis of CRC but might not be associated with tumor progression.

Keywords: Escherichia coli; carcinogenesis; colorectal cancer; microbiome; pks island.