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Association Between Fusobacterium nucleatum, Pathway Mutation, and Patient Prognosis in Colorectal Cancer

Annals of Surgical Oncology volume 25, pages 3389–3395 (2018)Cite this article

Abstract

Background

There is a close link between Fusobacterium nucleatum and colorectal cancer (CRC) tumorigenesis and chemoresistance. However, the genetic characteristics and clinical significance of CRC related with F. nucleatum remains unclear. This study evaluated the relationship between F. nucleatum, pathway mutation, and patient prognosis.

Methods

Fusobacterium nucleatum amount in the tumor tissue and adjacent normal tissue were measured by quantitative polymerase chain reaction in adjuvant (N = 128) and metastatic (N = 118) cohorts. Patients were divided into binary (F. nucleatum-high and F. nucleatum-low) according to F. nucleatum amount. Targeted next-generation sequencing of 40 genes included in the 5 critical pathways (WNT, P53, RTK-RAS, PI3 K, and TGF-β) was performed in the adjuvant cohort.

Results

Patients with MSI-H and CIMP-H had higher amount of F. nucleatum in tumor tissue. Fusobacterium nucleatum-high patients had higher rates of transition mutation and C to T (G to A) nucleotide change regardless of MSI status. In addition, mutation rate of AMER1 and ATM genes, and TGF-β pathway was higher in F. nucleatum-high patients. Fusobacterium nucleatum-high was associated with poor overall survival (OS) in the palliative cohort (26.4 vs. 30.7 months, p = 0.042). Multivariate analysis revealed F. nucleatum-high as an independent negative prognostic factor for OS [adjusted hazard ratio of 1.69 (95% confidence interval 1.04–2.75), p = 0.034]. However, F. nucleatum amount was not associated with recurrence in the adjuvant cohort.

Conclusions

F. nucleatum-high was associated with poor survival in metastatic CRC. In addition, we identified mutational characteristics of colorectal cancer according to F. nucleatum amount.

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Acknowledgment

This research was supported by the grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Nos. HI14C1277, HI13C2163).

Disclosure

The authors declare that they have no competing interests.

Author information

Affiliations

  1. Department of Internal Medicine, Seoul National University Hospital, 101 Daehang-Ro, Jongno-Gu, Seoul, 110-744, Korea

    Dae-Won Lee MD, Sae-Won Han MD, PhD & Tae-You Kim MD, PhD

  2. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

    Sae-Won Han MD, PhD, Jun-Kyu Kang MS, Hwang-Phill Kim PhD & Tae-You Kim MD, PhD

  3. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea

    Jun-Kyu Kang MS, Hwang-Phill Kim PhD & Tae-You Kim MD, PhD

  4. Department of Pathology, Seoul National University College of Medicine, Seoul, Korea

    Jeong Mo Bae MD, PhD, Jae-Kyung Won MD, PhD & Gyeong Hoon Kang MD, PhD

  5. Department of Surgery, Seoul National University Hospital, Seoul, Korea

    Seung-Yong Jeong MD, PhD & Kyu Joo Park MD, PhD

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  1. Dae-Won Lee MD
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  2. Sae-Won Han MD, PhD
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  6. Jae-Kyung Won MD, PhD
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  8. Kyu Joo Park MD, PhD
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  9. Gyeong Hoon Kang MD, PhD
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  10. Tae-You Kim MD, PhD
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Correspondence to Sae-Won Han MD, PhD.

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Lee, DW., Han, SW., Kang, JK. et al. Association Between Fusobacterium nucleatum, Pathway Mutation, and Patient Prognosis in Colorectal Cancer. Ann Surg Oncol 25, 3389–3395 (2018). https://doi.org/10.1245/s10434-018-6681-5

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  • DOI: https://doi.org/10.1245/s10434-018-6681-5

Keywords

  • Fusobacterium Nucleatum
  • Adjuvant Cohort
  • Independent Negative Prognostic Factor
  • CIMP Status
  • Tissue Fixation Methods