Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.
Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan.
Cancer Sci. 2024 Apr;115(4):1184-1195. doi: 10.1111/cas.16088. Epub 2024 Jan 31.
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.
肠微生物群与结直肠癌的发生和癌症进展之间存在显著关联。据报道,含有聚酮合酶(pks)岛的大肠杆菌(E. coli)通过产生 colibactin(一种聚酮肽遗传毒素)促进结直肠癌的发生。然而,pks E. coli 在结直肠癌(CRC)的起始、增殖和转移中的作用尚不清楚。我们研究了 pks E. coli 的临床意义,以阐明其在 CRC 中的功能。这项研究包括 413 名 CRC 患者。使用液滴数字 PCR 定量肿瘤组织和正常黏膜组织中的 pks E. coli。pks E. coli 在 0-I 期肿瘤组织中的丰度高于正常黏膜组织或 II-IV 期肿瘤组织中的丰度。肿瘤组织中 pks E. coli 的高丰度与肿瘤深度较浅显著相关(风险比[HR] = 5.0,95%置信区间[CI] = 2.3-11.3,p < 0.001),且无淋巴结转移(HR = 3.0,95%CI = 1.8-5.1,p < 0.001)。多变量逻辑分析显示,pks E. coli-低和 -阴性组与较短的 CRC 特异性生存(HR = 6.4,95% CI = 1.7-25.6,p = 0.005)和较短的无病生存(HR = 3.1,95% CI = 1.3-7.3,p = 0.01)显著相关,与 pks E. coli-高组相比。pks E. coli 在 0-I 期 CRC 中丰富,并与 CRC 预后相关。这些结果表明,pks E. coli 可能促进 CRC 的发生,但可能与肿瘤进展无关。