Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with and Its Subspecies .

BACKGROUND

() activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis.

METHODS

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.

RESULTS

, 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.

CONCLUSIONS

, and particularly subspecies , was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes.

IMPACT

Our findings identify the subspecies as negatively impacting colorectal cancer mortality, which may occur through a stage shift and its effect on chemoresistance.