Colibactin, a genotoxin produced byEscherichia colistrains harboring the polyketide synthetase (pks) gene cluster, causes DNA damage and somatic mutations.pks+E. coliis enriched in primary colorectal cancer (CRC) and is associated with clonal driver mutations, but its role in CRC liver metastasis is unclear. We assessed the association ofpks+E. coliin CRC liver metastasis tissues with systemic and local immune responses and the number of organs involved in recurrence using specimens and clinicopathological data from 239 patients with CRC liver metastasis who underwent metastasectomy. The levels ofpks+E. coliin fresh-frozen specimens were quantified as “very low” (<50th percentile), “low” (50th to 75th percentiles), and “high” (>75th percentile) using a digital PCR. Immunohistochemical analysis of tumor-infiltrating immune cells was performed using tissue microarrays. Systemic inflammation was evaluated using serum C-reactive protein (CRP) levels.pks+E. coliwas detected in 66.7% (157 of 239) liver metastasis tissues. Higher levels ofpks+E. coliwere associated with decreased serum CRP levels and reduced densities of CD4+cells and CD163+cells in the tumor-immune microenvironment. The “high”pks+E. coligroup had fewer metastatic organs involved than the “very low”pks+E. coligroup (mean number of organs: 1.00 vs. 1.23). These findings suggest thatpks+E. coliplay a modulating role in CRC metastasis.
大肠杆菌素是由携带聚酮合酶（pks）基因簇的大肠杆菌菌株产生的一种基因毒素，可导致DNA损伤和体细胞突变。pks阳性大肠杆菌在原发性结直肠癌（CRC）中富集，并与克隆驱动突变相关，但其在结直肠癌肝转移中的作用尚不明确。本研究利用239例接受转移灶切除术的结直肠癌肝转移患者的标本及临床病理数据，评估了肝转移组织中pks阳性大肠杆菌与全身及局部免疫反应以及复发累及器官数量的关联。通过数字PCR技术，将新鲜冷冻标本中pks阳性大肠杆菌的水平量化为“极低”（<50百分位数）、“低”（50至75百分位数）和“高”（>75百分位数）。利用组织微阵列对肿瘤浸润免疫细胞进行免疫组化分析，并通过血清C反应蛋白（CRP）水平评估全身炎症状态。结果显示，在66.7%（239例中的157例）的肝转移组织中检测到pks阳性大肠杆菌。较高水平的pks阳性大肠杆菌与血清CRP水平降低以及肿瘤免疫微环境中CD4+细胞和CD163+细胞密度减少相关。与“极低”pks阳性大肠杆菌组相比，“高”pks阳性大肠杆菌组患者复发时累及的转移器官数量更少（平均器官数：1.00 vs. 1.23）。这些发现表明，pks阳性大肠杆菌在结直肠癌转移过程中发挥调节作用。
肿瘤(癌症)患者之家