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Predictive Value of ERCC1, ERCC2, and XRCC Expression for Patients with Locally Advanced or Metastatic Gastric Cancer Treated with Neoadjuvant mFOLFOX-4 Chemotherapy

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Pathology & Oncology Research

Abstract

The dismal outcome in patients with locally advanced or metastatic gastric cancer (GC) highlights the need for effective systemic neoadjuvant chemotherapy to improve clinical results. This study evaluated the correlation between the expression of three DNA repair genes, namely the excision repair cross-complementing group 1 (ERCC1), excision repair cross-complementing group 2 (ERCC2), and X-ray repair cross-complementing protein 1 (XRCC1) and the clinical outcome of patients with locally advanced or metastatic GC treated with mFOLFOX-4 neoadjuvant chemotherapy. Fifty-eight patients with histologically confirmed locally advanced or metastatic GC following neoadjuvant mFOLFOX-4 chemotherapy were enrolled between January 2009 and January 2018. We analyzed clinicopathological features and ERCC1, ERCC2, and XRCC1 expression to identify potential predictors of clinical response. Among the 58 patients, 16 (27.6%) were categorized into the response group (partial response) and 42 into the nonresponse group (stable disease in 24 patients and progressive disease in 18 patients). A multivariate analysis showed that ERCC1 overexpression (P = 0.003), ERCC2 overexpression (P = 0.049), and either ERCC1 or ERCC2 overexpression (P = 0.002) were independent predictors of response following mFOLFOX-4 neoadjuvant chemotherapy. Additionally, ERCC1 and ERCC2 overexpression did not only predict the response but also progression-free survival (both P < 0.05) and overall survival (both P < 0.05). ERCC1 and ERCC2 overexpression are promising predictive biomarkers for patients with locally advanced or metastatic GC receiving neoadjuvant mFOLFOX-4 chemotherapy and the potential clinical implication is mandatory for further investigation.

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Acknowledgements

This work was supported by grants through funding from the Ministry of Science and Technology (MOST108-2321-B-037-001, MOST107-2321-B-037-003, MOST107-2314-B-037-116, MOST107-2314-B-037-022-MY2, MOST107-2314-B-037-023-MY2) and the Ministry of Health and Welfare (MOHW107-TDU-B-212-123006, MOHW107-TDU-B-212-114026B, MOHW108-TDU-B-212-133006) funded by Health and welfare surcharge of tobacco products), and the Kaohsiung Medical University Hospital (KMUH107-7R28, KMUH107-7R29, KMUH107-7R30, KMUH107-7M22, KMUH107-7M23, KMUHS10701, KMUHS10706, KMUHS10710). In addition, this study was supported by the Grant of Biosignature in Colorectal Cancers, Academia Sinica, Taiwan, R.O.C.

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Authors and Affiliations

  1. Division of Trauma and Surgical Critical Care, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yung-Sung Yeh

  2. Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou 1st Road, San-Ming District, Kaohsiung, 807, Taiwan

    Yung-Sung Yeh, Hsiang-Lin Tsai, Ching-Wen Huang, Cheng-Jen Ma, Wei-Chih Su & Jaw-Yuan Wang

  3. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yung-Sung Yeh, Wei-Chih Su & Jaw-Yuan Wang

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

    Yi-Ting Chen

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

    Yi-Ting Chen

  6. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yi-Ting Chen, Ching-Wen Huang, Chun-Ming Huang & Jaw-Yuan Wang

  7. Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hsiang-Lin Tsai, Ching-Wen Huang & Jaw-Yuan Wang

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

    Chun-Ming Huang & Ming-Yii Huang

  9. Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Ming-Yii Huang

  10. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Huang-Ming Hu & Chien-Yu Lu

  11. Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Huang-Ming Hu & Chien-Yu Lu

  12. Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan

    Jaw-Yuan Wang

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  1. Yung-Sung Yeh
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Correspondence to Jaw-Yuan Wang.

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Abstract was presented as a poster in 2017 NCRI Cancer Conference and published in Abstract in European Journal of Surgical Oncology 2017; 43: 2216.

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Yeh, YS., Chen, YT., Tsai, HL. et al. Predictive Value of ERCC1, ERCC2, and XRCC Expression for Patients with Locally Advanced or Metastatic Gastric Cancer Treated with Neoadjuvant mFOLFOX-4 Chemotherapy. Pathol. Oncol. Res. 26, 1105–1116 (2020). https://doi.org/10.1007/s12253-019-00666-5

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