Cancer Biology and Therapeutics Laboratory, UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, D04 V1W8, Ireland.
Infections and Cancer Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120, Heidelberg, Germany.
Dig Dis Sci. 2023 Aug;68(8):3300-3311. doi: 10.1007/s10620-023-08001-4. Epub 2023 Jun 20.
Streptococcus gallolyticus subspecies gallolyticus (SGG) and Fusobacterium (F.) nucleatum have been implicated in colorectal carcinogenesis. Here, the association of immune responses to bacterial exposure with advancing stages of colorectal neoplasia was assessed by multiplex serology.
Immunoglobulin (Ig) A and G antibody responses to eleven proteins each of F. nucleatum and SGG were measured in plasma of controls (n = 100) and patients with colorectal cancer (CRC, n = 25), advanced adenoma (n = 82), or small polyps (n = 85). Multivariable logistic regression was used to evaluate the association of bacterial sero-positivity with colorectal neoplasia. In a cohort subset with matched data (n = 45), F. nucleatum sero-positivity was correlated with bacterial abundance in both neoplastic and matched normal tissue.
IgG sero-positivity to Fn1426 of F. nucleatum was associated with an increased CRC risk (OR = 4.84; 95% CI 1.46-16.0), while IgA sero-positivity to any SGG protein or specifically Gallo0272 and Gallo1675 alone was associated with increased advanced adenoma occurrence (OR = 2.02, 95% CI 1.10-3.71; OR = 2.67, 95% CI 1.10-6.46; and OR = 6.17, 95% CI 1.61-23.5, respectively). Only F. nucleatum abundance in the normal mucosa positively correlated with the IgA response to the Fn1426 antigen (Correlation coefficient (r) = 0.38, p < 0.01).
Antibody responses to SGG and F. nucleatum were associated with occurrence of colorectal adenomas and CRC, respectively. Further studies are needed to clarify the role these microbes or the immune response to their antigens may have in colorectal carcinogenesis stages.
酿脓链球菌亚种（SGG）和具核梭杆菌（F. nucleatum）已被认为与结直肠癌变有关。在这里，通过多重血清学评估了对细菌暴露的免疫反应与结直肠肿瘤进展阶段的关系。
在对照组（n=100）和结直肠癌（CRC，n=25）、高级腺瘤（n=82）或小息肉（n=85）患者的血浆中测量了针对 F. nucleatum 和 SGG 的每种 11 种蛋白的 IgA 和 IgG 抗体反应。使用多变量逻辑回归来评估细菌血清阳性与结直肠肿瘤的关联。在具有匹配数据的队列子集中（n=45），F. nucleatum 血清阳性与肿瘤和匹配正常组织中的细菌丰度相关。
Fn1426 的 F. nucleatum IgG 血清阳性与 CRC 风险增加相关（OR=4.84；95%CI 1.46-16.0），而针对任何 SGG 蛋白或单独针对 Gallo0272 和 Gallo1675 的 IgA 血清阳性与高级腺瘤发生增加相关（OR=2.02，95%CI 1.10-3.71；OR=2.67，95%CI 1.10-6.46；OR=6.17，95%CI 1.61-23.5）。仅正常黏膜中 F. nucleatum 的丰度与针对 Fn1426 抗原的 IgA 反应呈正相关（相关系数（r）=0.38，p<0.01）。
SGG 和 F. nucleatum 的抗体反应分别与结直肠腺瘤和 CRC 的发生有关。需要进一步的研究来阐明这些微生物或其抗原的免疫反应可能在结直肠癌变阶段中所起的作用。
