Prognostic Impact of Fusobacterium nucleatum Depends on Combined Tumor Location and Microsatellite Instability Status in Stage II/III Colorectal Cancers Treated with Adjuvant Chemotherapy.

Background: This study aimed to investigate the prognostic impact of intratumoral Fusobacterium nucleatum in colorectal cancer (CRC) treated with adjuvant chemotherapy.

Materials and Methods: F. nucleatum DNA was quantitatively measured in a total of 593 CRC tissues retrospectively collected from surgically resected specimens of stage III or high-risk stage II CRC patients who had received curative surgery and subsequent oxaliplatin-based adjuvant chemotherapy (either FOLFOX or CAPOX). Each case was classified into one of the three categories: F. nucleatum‒high, ‒low, or ‒negative.

Results: No significant differences in survival were observed between the F. nucleatum‒high and ‒low/negative groups in the 593 CRCs (p=.671). Subgroup analyses according to tumor location demonstrated that disease-free survival was significantly better in F. nucleatum‒high than in ‒low/negative patients with non-sigmoid colon cancer (including cecal, ascending, transverse, and descending colon cancers; n=219; log-rank p=.026). In multivariate analysis, F. nucleatum was determined to be an independent prognostic factor in non-sigmoid colon cancers (hazard ratio, 0.42; 95% confidence interval, 0.18 to 0.97; p=.043). Furthermore, the favorable prognostic effect of F. nucleatum‒high was observed only in a non-microsatellite instability-high (non-MSI-high) subset of non-sigmoid colon cancers (log-rank p=0.014), but not in a MSI-high subset (log-rank p=0.844), suggesting that the combined status of tumor location and MSI may be a critical factor for different prognostic impacts of F. nucleatum in CRCs treated with adjuvant chemotherapy.

Conclusion: Intratumoral F. nucleatum load is a potential prognostic factor in a non-MSI-high/non-sigmoid/non-rectal cancer subset of stage II/III CRCs treated with oxaliplatin-based adjuvant chemotherapy.