J Pathol Transl Med.  2019 Jan;53(1):40-49. 10.4132/jptm.2018.11.29.

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

Affiliations
  • 1Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea. junghokim@snuh.org, ghkang@snu.ac.kr
  • 2Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Abstract

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

Keyword

Colorectal neoplasms; Fusobacterium; Gastrointestinal microbiome; Prognosis

MeSH Terms

Chemotherapy, Adjuvant*
Colon, Descending
Colonic Neoplasms
Colorectal Neoplasms*
Disease-Free Survival
DNA
Fusobacterium nucleatum*
Fusobacterium*
Gastrointestinal Microbiome
Humans
Microsatellite Instability*
Microsatellite Repeats*
Multivariate Analysis
Prognosis
Retrospective Studies
DNA

Figure

  • Fig. 1. Different proportions of Fusobacterium nucleatum–high vs F. nucleatum–low/negative colorectal cancers according to tumor location bowel subsites.

  • Fig. 2. Kaplan-Meier survival analysis, including subgroup analysis according to tumor location. (A) No significant difference in disease-free survival was evident between Fusobacterium nucleatum–high and –low/negative subgroups in the overall 593 stage II/III colorectal cancer patients treated with oxaliplatin-based adjuvant chemotherapy. (B) The F. nucleatum–high subgroup was significantly associated with better disease-free survival in non-sigmoid colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy (n=219). (C) In sigmoid colon and rectal cancer patients treated with oxaliplatin-based adjuvant chemotherapy (n=374), the F. nucleatum–high subgroup shows a tendency toward worse disease-free survival without statistical significance.

  • Fig. 3. Kaplan-Meier survival analysis, including subgroup analysis according to combined tumor location and microsatellite instability (MSI) status. (A) The Fusobacterium nucleatum–high subgroup was significantly associated with better disease-free survival in an MSS/MSI-low subset of non-sigmoid colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy (n=185). (B) No significant survival difference according to F. nucleatum status was observed in an MSI-high subset of non-sigmoid colon cancer patients treated with oxaliplatinbased adjuvant chemotherapy (n=31). (C) There is a tendency toward worse survival in the F. nucleatum–high subgroup without statistical significance in an MSS/MSI-low subset of sigmoid colon or rectal cancer patients treated with oxaliplatin-based adjuvant chemotherapy (n= 360). (D) No significant survival difference according to F. nucleatum status was observed in an MSI-high subset of sigmoid colon or rectal cancer patients treated with oxaliplatin-based adjuvant chemotherapy (n=9).


Cited by  1 articles

Prognostic and clinicopathological significance of Fusobacterium nucleatum in colorectal cancer: a systemic review and meta-analysis
Younghoon Kim, Nam Yun Cho, Gyeong Hoon Kang
J Pathol Transl Med. 2022;56(3):144-151.    doi: 10.4132/jptm.2022.03.13.


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