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Medical Oncology

, 35:145 | Cite as

Genetic variations using whole-exome sequencing might predict response for neoadjuvant chemoradiotherapy in locally advanced rectal cancer

  • In Hee Lee
  • Keunsoo Kang
  • Byung Woog Kang
  • Soo jung Lee
  • Woo Kyun Bae
  • Jun Eul Hwang
  • Hye Jin Kim
  • Su Yeon Park
  • Jun Seok Park
  • Gyu Seog Choi
  • Jong Gwang Kim
Original Paper

Abstract

A good pathologic response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is associated with a better prognosis. However, there is no effective method to predict CRT response in LARC patients. Therefore, this study used whole-exome sequencing (WES) to identify novel biomarker predicting CRT benefit in LARC. Two independent tumor tissue sets were used to evaluate the genetic differences between the good CRT response group (15 patients achieved a pathologic complete response (pCR)) and the poor CRT response group (15 patients with pathologic stage III). After applying WES to the discovery set of 30 patients, additional samples (n = 67) were genotyped for candidate variants using TaqMan or Sanger sequencing for validation. Overall, this study included a total of 97 LARC patients. In the discovery and validation set, there was no known genetic mutation to predict response between two groups, while five candidate variants (BCL2L10 rs2231292, DLC1 rs3816748, DNAH14 rs3105571, ITIH5 rs3824658, and RAET1L rs912565) were found to be significantly associated with pCR. In the dominant model, the GC/CC genotype of DLC1 rs3816748 (p = 0.032), AC/CC genotype of DNAH14 rs3105571 (p = 0.009), and TT genotype of RAET1 rs912565 (p < 0.0001) were associated with a higher pCR rate. In the recessive model, BCL2L10 rs2231292 (p = 0.036) and ITIH5 rs3824658 (p = 0.003) were significantly associated with pCR. In the co-dominant model, 4 candidate variants (DLC1 rs3816748, DNAH14 rs3105571, ITIH5 rs3824658, and RAET1L rs912565) were significantly correlated with pCR. However, none of the candidate variants was associated with relapse-free or overall survival. The present results suggest that genetic variations of the BCL2L10 rs2231292, DLC1 rs3816748, DNAH14 rs3105571, ITIH5 rs3824658, and RAET1L rs912565 genes can be used as biomarkers predicting the CRT response for patients with LARC.

Keywords

Next-generation sequencing Whole-exome sequencing Pathologic complete response Neoadjuvant chemoradiotherapy Locally advanced rectal cancer 

Notes

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2014R1A5A2009242) and Korean Cancer Foundation (K20170519).

Compliance with ethical standards

Conflict of interest

The authors declared no conflicts of interest.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Kyungpook National University Hospital Institutional Review Board (IRB).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12032_2018_1202_MOESM1_ESM.docx (51 kb)
Supplementary material 1 (DOCX 51 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • In Hee Lee
    • 1
  • Keunsoo Kang
    • 2
  • Byung Woog Kang
    • 1
  • Soo jung Lee
    • 1
  • Woo Kyun Bae
    • 3
  • Jun Eul Hwang
    • 3
  • Hye Jin Kim
    • 4
  • Su Yeon Park
    • 4
  • Jun Seok Park
    • 4
  • Gyu Seog Choi
    • 4
  • Jong Gwang Kim
    • 1
  1. 1.Department of Oncology/HematologySchool of Medicine, Kyungpook National University, Kyungpook National University Chilgok HospitalDaeguRepublic of Korea
  2. 2.Department of Microbiology, College of Natural SciencesDankook UniversityCheonanRepublic of Korea
  3. 3.Department of Hematology-OncologyChonnam National University Medical SchoolGwangjuRepublic of Korea
  4. 4.Department of SurgerySchool of Medicine, Kyungpook National University, Kyungpook National University Chilgok HospitalDaeguRepublic of Korea

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