Evaluation of antibody level against Fusobacterium nucleatum in the serological diagnosis of colorectal cancer

Abstract

Fusobacterium nucleatum (F. nucleatum, Fn) is associated with the colorectal cancer (CRC). Fn-infection could induce significant levels of serum Fn-specific antibodies in human and mice. The objective of this study was to identify Fn-infection that elicit a humoral response in patients with CRC and evaluate the diagnostic performance of serum anti-Fn antibodies. In this work, we showed the mean absorbance value of anti-Fn-IgA and -IgG in the CRC group were significantly higher than those in the benign colon disease group and healthy control group (P < 0.001). The sensitivity and specificity of ELISA for the detection of anti-Fn-IgA were 36.43% and 92.71% based on the optimal cut-off. The combination of anti-Fn-IgA and carcino-embryonic antigen (CEA) was better for diagnosing CRC (Sen: 53.10%, Spe: 96.41%; AUC = 0.848). Furthermore, combining anti-Fn-IgA with CEA and carbohydrate antigen 19-9 (CA19-9) (Sen: 40.00%, Spe: 94.22%; AUC = 0.743) had the better ability to classify CRC patients with stages I-II. These results suggested that Fn-infection elicited high level of serum anti-Fn antibodies in CRC patients, and serum anti-Fn-IgA level may be a potential diagnosing biomarker for CRC. Serum anti-Fn-IgA in combination with CEA and CA19-9 increases the sensitivity of detecting early CRC.

Immunization with alkyl hydroperoxide reductase subunit C reduces Fusobacterium nucleatum load in the intestinal tract

“…Previous studies have shown that Fn induced a significant humoural immune response in chronic oral infection 12 , 15 . In a recent study, we showed that Fn infection elicited high-level serum antibody to Fn in CRC patients 16 . Using the sera from CRC patients to probe the bacteria protein extract, we identified a strong reactive antigen, alkyl hydroperoxide reductase subunit C (AhpC), which triggers the anti-Fn immune response 16 .…”

“…In a recent study, we showed that Fn infection elicited high-level serum antibody to Fn in CRC patients 16 . Using the sera from CRC patients to probe the bacteria protein extract, we identified a strong reactive antigen, alkyl hydroperoxide reductase subunit C (AhpC), which triggers the anti-Fn immune response 16 . The AhpC protein is a member of the highly conserved family of peroxiredoxins that catalyse the reduction of hydroperoxides for protection against oxygen radical damage 17 .…”

Are we any closer to screening for colorectal cancer using microbial markers?A critical review

“…A Japanese study demonstrated high positive predictive power for CRC of high-copy number of F. nucleatum DNA detected by spe-cies-specific PCR (ref. 61 ) and a Chinese group reported increased levels of anti-F. nucleatum IgA antibodies in serum of CRC patients 62 . Another pilot study tested analytical approaches to detection of diverse bacterial genes in stool samples that may indicate the risk of CRC (ref.…”

The antibody/microbiota interface in health and disease

“…[88][89][90] A prospective study recently associated a commensal candidate, Streptococcus gallolyticus subspecies gallolyticus (SGG) with the risk to develop CRC, since anti-SGG IgG were more frequently present in individuals who developed cancer later in life (Table 2). 91 Although a causative link between the presence of such species and CRC has not been demonstrated, certain anti-commensal IgA 92 or IgG 91 reactivities might constitute potential diagnostic biomarkers for CRC. The detection of anti-commensal IgG might also offer novel opportunities for predicting immunotherapy efficacy in the treatment of cancers.…”