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Relationship Between Expression of Proteins ERCC1, ERCC2, and XRCC1 and Clinical Outcomes in Patients with Rectal Cancer Treated with FOLFOX-Based Preoperative Chemoradiotherapy

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Abstract

Background

Platinum resistance enhances DNA damage repair through nucleotide excision repair mechanisms involving the excision repair cross-complementing group 1 (ERCC1), X-ray cross-complementing group 1 (XRCC1), and excision repair cross-complementing group 2 (ERCC2). We evaluated the correlation between the expression of these three DNA repair genes and clinical outcomes in patients with rectal cancer receiving FOLFOX-based preoperative chemoradiotherapy (CRT).

Methods

Using immunohistochemistry, we examined the expression of ERCC1, ERCC2, and XRCC1 in pre-CRT cancer tissues from 86 patients with rectal cancer who had undergone curative resection and preoperative CRT with FOLFOX-4 to identify potential predictors of clinical outcomes.

Results

Following CRT, 57 and 29 patients were classified as responders (pathological tumor regression grade TRG 0 and TRG 1) and poor responders (TRG 2 and TRG 3), respectively. The multivariate analysis revealed that ERCC1 overexpression was correlated with a poor CRT response [p < 0.0001; odds ratio (OR), 9.397; 95% confidence interval (CI) 2.721–32.457]. Furthermore, a poor response to CRT (pathological TRG of 2–3) (p = 0.18; OR 5.685; 95% CI 1.349–23.954) and abnormal pre-CRT serum carcinoembryonic antigen levels (>5 ng/mL) (p = 0.03; OR 6.288; 95% CI 1.198–33.006) were independent predictors of postoperative relapse. By contrast, ERCC2 and XRCC1 expression did not play predictive roles in the analyzed patients.

Conclusions

ERCC1 overexpression is associated with a poor preoperative CRT response in patients with rectal cancer receiving FOLFOX-based preoperative CRT. ERCC1 is a potential biomarker for identifying patients who can benefit from customized treatment programs.

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Acknowledgements

This work was supported by Grants from the Excellence for Cancer Research Center Grant, funding by the Ministry of Science and Technology (MOST103-2314-B-037-010-MY3, MOST105-2325-B-037-001) and the Ministry of Health and Welfare (MOHW106-TDU-B-212-144007), Health and Welfare Surcharge of Tobacco Products, Taiwan, Republic of China, and Kaohsiung Medical University Hospital (KMUH102-2M69, KMUH104-4M51, KMUHS10505, KMUHS10518, KMUHS10522, KMUHGCRC2016002). The study is supported by Kaohsiung Medical University “Aim for the Top University Grant”, the Center for Biomarkers and Biotech Drugs, (KMU-TP105C01, KMU-TP105C02, KMU-TP105C11, KMU-TP106005, KMU-TP105A14, K MU-DK106005, SH000113 [Give2Asia]) and the Grant of Biosignature in Colorectal Cancers, Academia Sinica, Taiwan.

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Author notes

  1. Ming-Yii Huang and Joh-Jong Huang equally contributed to the current study.

Authors and Affiliations

  1. Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Ming-Yii Huang & Chun-Ming Huang

  2. Department of Radiation Oncology, Faculty of Medicine, Graduate Institute of Medicine, College of Medicine, Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan

    Ming-Yii Huang

  3. Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Joh-Jong Huang

  4. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Chih-Hung Lin & Chee-Yin Chai

  5. Department of Pathology, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chih-Hung Lin & Chee-Yin Chai

  6. Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hsiang-Lin Tsai & Ching-Wen Huang

  7. Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hsiang-Lin Tsai & Ching-Wen Huang

  8. Department of Nuclear Medicine, Kaohsiung Medical University Hospital, No. 100 Tzyou 1st Road, Kaohsiung, 807, Taiwan

    Chia-Yang Lin

  9. Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Jaw-Yuan Wang

  10. Department of Surgery, Graduate Institute of Clinical Medicine, College of Medicine, Center for Natural products and Drug Development, Center for Biomarkers and Biotech Drugs and Center for Environmental Medicine, Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung, 807, Taiwan

    Jaw-Yuan Wang

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  1. Ming-Yii Huang
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Correspondence to Chia-Yang Lin or Jaw-Yuan Wang.

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Huang, MY., Huang, JJ., Huang, CM. et al. Relationship Between Expression of Proteins ERCC1, ERCC2, and XRCC1 and Clinical Outcomes in Patients with Rectal Cancer Treated with FOLFOX-Based Preoperative Chemoradiotherapy. World J Surg 41, 2884–2897 (2017). https://doi.org/10.1007/s00268-017-4070-z

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