Ming-Yii Huang1,2, Joh-Jong Huang3, Chun-Ming Huang1, Chih-Hung Lin4,5, Hsiang-Lin Tsai6,7, Ching-Wen Huang6,7, Chee-Yin Chai4,5, Chia-Yang Lin8, Jaw-Yuan Wang9,10. 1. Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 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. 3. Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 4. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 5. Department of Pathology, Kaohsiung Medical University, Kaohsiung, Taiwan. 6. Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 7. Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan. 8. Department of Nuclear Medicine, Kaohsiung Medical University Hospital, No. 100 Tzyou 1st Road, Kaohsiung, 807, Taiwan. 950195@ms.kmuh.org.tw. 9. Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. cy614112@ms14.hinet.net. 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. cy614112@ms14.hinet.net.
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.
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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