Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington.
Cancer Epidemiol Biomarkers Prev. 2022 Jan;31(1):210-220. doi: 10.1158/1055-9965.EPI-21-0463. Epub 2021 Nov 4.
() activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis.
We characterized and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of , , and bacterial genes in tumors from 1,994 patients with colorectal cancer and assessed associations between presence and clinical characteristics, colorectal cancer-specific mortality, and somatic mutations.
, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies . Presence of was associated with higher colorectal cancer-specific mortality (HR, 1.97; = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07-3.45; = 0.029). Only subspecies , the main subspecies detected (65.8%), was associated with colorectal cancer-specific mortality (HR, 2.16; = 0.0016), subspecies and were not (HR, 1.07; = 0.86). Additional adjustment for tumor stage suggests that the effect of on mortality is partly driven by a stage shift. Presence of was associated with microsatellite instable tumors, tumors with exonuclease domain mutations, and mutations, and suggestively associated with mutations.
, and particularly subspecies , was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes.
Our findings identify the subspecies as negatively impacting colorectal cancer mortality, which may occur through a stage shift and its effect on chemoresistance.
（）激活致癌信号通路并引发炎症，从而促进结直肠癌的发生。
我们对结直肠肿瘤中的 和其亚种进行了特征分析，并研究了与肿瘤特征和结直肠癌特异性生存的关联。我们对 1994 例结直肠癌患者的肿瘤进行了 、 和细菌 基因的深度测序，并评估了 存在与临床特征、结直肠癌特异性死亡率以及体细胞突变之间的关联。
在 10.3%的肿瘤中检测到的 ，在右侧和晚期肿瘤中的比例更高，特别是亚种 。 的存在与更高的结直肠癌特异性死亡率相关（HR，1.97； = 0.0004）。这种关联仅限于非高突变、微卫星稳定的肿瘤（HR，2.13； = 0.0002）和接受化疗的肿瘤[HR，1.92；置信区间（CI），1.07-3.45； = 0.029]。只有主要检测到的亚种 与结直肠癌特异性死亡率相关（HR，2.16； = 0.0016），亚种 和 则没有（HR，1.07； = 0.86）。对肿瘤分期的进一步调整表明， 对死亡率的影响部分是由分期转移引起的。 的存在与微卫星不稳定的肿瘤、具有外切酶结构域突变的肿瘤以及 突变相关，并且与 突变具有提示性关联。
和特别是亚种 与结直肠癌特异性死亡率升高相关，这可能是通过分期转移和对化疗耐药性的影响来实现的。
我们的研究结果确定了亚种 作为结直肠癌死亡率的负相关因素，这可能是通过分期转移及其对化疗耐药性的影响来实现的。
