Serology of Streptococcus gallolyticus subspecies gallolyticus and its association with colorectal cancer and precursors

Abstract

Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC) and its precursors. A previous case-control study measured antibody responses to SGG pilus proteins Gallo2178 and Gallo2179 and identified significant associations with a small fraction of CRC cases. We aimed at replicating and expanding these findings in an independent study including additional SGG antigens and explored the association with precancerous lesions. We applied multiplex serology to measure antibodies to eleven SGG proteins in serum samples of a screening colonoscopy trial (BliTz study) including participants diagnosed with either non-advanced adenoma (NAA, n = 30), advanced adenoma (AA, n = 100), CRC (n = 50) or controls (n = 228). In addition, we analyzed CRC samples (n = 318) from patients recruited in a clinical setting (DACHSplus study). The association of antibody responses to SGG pilus proteins Gallo2178 and Gallo2179 with CRC was replicated with 4% positive DACHSplus cases compared to 0% positive BliTz controls. Positivity to two or more proteins of a newly defined panel of six SGG markers was significantly associated with CRC in the DACHSplus study (OR: 1.81, 95% CI: 1.07-3.06). Odds for CRC, AA and NAA in the BliTz study were also increased with antibody responses to SGG, and the association was significant for NAA (OR: 2.98, 95% CI: 1.18-7.57). Antibody responses to SGG are associated with CRC and its precursors. The newly identified SGG six-marker panel and associations found with precancerous lesions should be further explored.

Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer

“…The gut bacterium Streptococcus gallolyticus subspecies gallolyticus (SGG) has been associated with colorectal cancer (CRC), but whether this association exists pre-diagnostically remains unknown. 16 The 6marker panel demonstrated a higher specificity for CRC risk compared to positivity towards any one of the 11 SGG proteins included in the multiplex serology panel. They demonstrate a positive association of antibody responses to SGG proteins with CRC risk in pre-diagnostic samples, implicating SGG serology as a new marker for risk of developing CRC.…”

“…16 The distribution of antibody responses (MFI) to all 11 SGG proteins among controls was skewed towards low MFI, especially when compared to the outer membrane protein (OMP) of Helicobacter pylori, analyzed in the same experimental setting ( Fig. 16 The distribution of antibody responses (MFI) to all 11 SGG proteins among controls was skewed towards low MFI, especially when compared to the outer membrane protein (OMP) of Helicobacter pylori, analyzed in the same experimental setting ( Fig.…”

“…1): the upper quartile of antibody responses does not exceed 100 MFI for any of the SGG antigens, whereas Cancer Epidemiology Butt et al this antibody level was exceeded by 50% of the control sera to H. pylori OMP. 16 This algorithm was also applied here as a second definition for SGG positivity. The technical minimum cut-off was 30 MFI (Table 1).…”

“…In the 1970s, it was found that infective endocarditis What's new? [11][12][13][14] We previously applied multiplex serology, a fluorescent bead-based high-throughput technology allowing serological typing of several antigens in one reaction, 15 to analyze antibody responses to 11 SGG proteins in a German CRC casecontrol study. Here the authors performed a serological study in a prospective setting with samples from the European Prospective Investigation into Nutrition and Cancer (EPIC).…”

“…Here the authors performed a serological study in a prospective setting with samples from the European Prospective Investigation into Nutrition and Cancer (EPIC). 16 These previous findings were based on traditional case-control designs where blood samples were obtained post-diagnosis. caused by bacteria belonging to the S. bovis complex, [5][6][7] and later more specifically by the subspecies SGG, 8 co-occurred with the presence of colorectal adenoma.…”