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J Pathol Transl Med. 2018 Dec 26. doi: 10.4132/jptm.2018.11.29. [Epub ahead of print]

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

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Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.



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.


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.


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.


Colorectal neoplasms; Fusobacterium; Gastrointestinal microbiome; Prognosis

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