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Annals of Surgical Oncology

, Volume 25, Issue 11, pp 3389–3395 | Cite as

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

  • Dae-Won Lee
  • Sae-Won HanEmail author
  • Jun-Kyu Kang
  • Jeong Mo Bae
  • Hwang-Phill Kim
  • Jae-Kyung Won
  • Seung-Yong Jeong
  • Kyu Joo Park
  • Gyeong Hoon Kang
  • Tae-You Kim
Translational Research and Biomarkers

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.

Notes

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.

Supplementary material

10434_2018_6681_MOESM1_ESM.docx (560 kb)
Supplementary material 1 (DOCX 560 kb)

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Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Dae-Won Lee
    • 1
  • Sae-Won Han
    • 1
    • 2
    Email author
  • Jun-Kyu Kang
    • 2
    • 3
  • Jeong Mo Bae
    • 4
  • Hwang-Phill Kim
    • 2
    • 3
  • Jae-Kyung Won
    • 4
  • Seung-Yong Jeong
    • 5
  • Kyu Joo Park
    • 5
  • Gyeong Hoon Kang
    • 4
  • Tae-You Kim
    • 1
    • 2
    • 3
  1. 1.Department of Internal MedicineSeoul National University HospitalSeoulKorea
  2. 2.Cancer Research InstituteSeoul National University College of MedicineSeoulKorea
  3. 3.Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and TechnologySeoul National UniversitySeoulKorea
  4. 4.Department of PathologySeoul National University College of MedicineSeoulKorea
  5. 5.Department of SurgerySeoul National University HospitalSeoulKorea

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