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

• Published in: World journal of surgery Vol. 41; no. 11; pp. 2884 - 2897
• Main Authors: Huang, Ming-Yii, Huang, Joh-Jong, Huang, Chun-Ming, Lin, Chih-Hung, Tsai, Hsiang-Lin, Huang, Ching-Wen, Chai, Chee-Yin, Lin, Chia-Yang, Wang, Jaw-Yuan
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.11.2017; Springer Nature B.V
• Subjects: Abdominal Surgery; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers; Cancer; Carcinoembryonic antigen; Cardiac Surgery; Chemoradiotherapy; Chemoradiotherapy, Adjuvant; Chemotherapy; Clinical outcomes; Colorectal cancer; Confidence intervals; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; DNA-Binding Proteins - metabolism; Endonucleases - metabolism; ERCC1 protein; Female; Fluorouracil - therapeutic use; Gene expression; General Surgery; Health risk assessment; Humans; Immunohistochemistry; Leucovorin - therapeutic use; Male; Medicine; Medicine & Public Health; Middle Aged; Multivariate analysis; Nucleotide excision repair; Organoplatinum Compounds - therapeutic use; Original Scientific Report; Patients; Platinum; Proteins; Quality; Radiation therapy; Rectal Neoplasms - metabolism; Rectal Neoplasms - surgery; Rectal Neoplasms - therapy; Rectum; Regression analysis; Repair; Statistical analysis; Surgery; Thoracic Surgery; Tissues; Treatment Outcome; Vascular Surgery; X-ray Repair Cross Complementing Protein 1 - metabolism; Xeroderma Pigmentosum Group D Protein - metabolism; XRCC1 protein
• ISSN: 0364-2313; 1432-2323
• DOI: 10.1007/s00268-017-4070-z

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.