摘要
目的明确鼻咽癌铂类同期放化疗疗效与肿瘤组织中DNA切除修复交叉互补基因1(excision repair cross-complementing gene1, ERCC1)mRNA表达水平的关系。方法选取2012年6月至2013年6月在广西医科大学第四附属医院肿瘤科经活检诊断为鼻咽低分化鳞癌的初治患者,放化疗前通过RT-PCR测量肿瘤组织中ERCC1 mRNA表达水平,所有患者均接受顺铂单药同期放化疗,治疗结束3个月后复查,评估疗效,分析铂类药物化疗短期疗效与ERCC1 mRNA表达水平间的关系。结果共78例患者纳入研究且可评价,其中完全缓解占65.38%,部分缓解占24.36%,疾病稳定占5.13%,疾病进展占5.13%;有效率89.74%,疾病控制率94.87%。ERCC1 mRNA在肿瘤组织的平均表达水平为1.216,患者的年龄、性别和TNM分期与ERCC1 mRNA表达水平间差异均无统计学意义(P>0.05)。放化疗前肿瘤组织中ERCC1 mRNA低表达的治疗有效率明显高于高表达者(P<0.05)。结论 ERCCl mRNA在鼻咽癌组织中的表达水平与铂类同期放化疗短期疗效间呈负相关关系,可预测铂类同期放化疗治疗局部晚期鼻咽癌的效果。
Objective To explore the relationship between the efficacy of platinum concurrent chemotherapy in advanced nasopharyngeal carcinoma and the expression level of excision repair cross-complementing gene1(ERCC1) mRNA in tumor tissue.Methods A total of 87 untreated patients who were diagnosed as poorly differentiated squamous cell carcinoma of the nasopharyngeal tissue by biopsy from June 2012 to June 2013 in the Fourth Affiliated Hospital of Guangxi Medical University. The expression of ERCC1 mRNA in tumor tissue was measured by reverse transcription polymerase chain reaction(RT-PCR) before chemotherapy. All the patients received Cisplatin-based concurrent chemoradiotherapy. The efficacy was evaluated after the treatment of three months.Results A total of 78 patients were included in this study whose CR, PR, SD and PD reached 65.38%, 24.36%, 5.13% and 5.13% respectively. Effective rate(RR) was 89.74%, and disease control rate(DCR) was 94.87%. The average expression level of ERCC1 mRNA was 1.216. There was no significant difference between the age, sex, TNM stage and ERCC1 mRNA expression. The effective rate of ERCC1 mRNA low expression in tumor tissues before treatment was significantly higher than that of high expression group(P<0.05).Conclusions The expression level of ERCC1 mRNA in nasopharyngeal carcinoma negatively correlates with the short-term efficacy of platinum-based concurrent radiochemotherapy for locally advanced nasopharyngeal carcinoma, which might be a useful predictive marker.
引文
[1] van Duin M, de Wit J, Odijk H, et al. Molecular characterization of the human excision repair gene ERCC-1: cDNA cloning and amino acid homology with the yeast DNA repair gene RAD10[J]. Cell, 1986,44(6):913-923.
[2] Olaussen KA, Postel-Vinay S. Predictors of chemotherapy efficacy in non-small-cell lung cancer:a challenging landscape[J].Ann Oncol,2016,27(11):2004-2016.
[3] Khrunin AV, Moisseev A, Gorbunova V, et al. Genetic polymorphisms and the efficacy and toxicity of cisplatin-based chemotherapy in ovarian cancer patients[J]. Pharmacogenomics J, 2010,10(1):54-61.
[4] 殷蔚伯,徐子豪,徐国镇,等.肿瘤放射治疗学[M]. 北京:中国协和医科大学出版社,2008:443-484.
[5] Lee AW, Ma BB, Ng WT, et al. Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective[J]. J Clin Oncol, 2015,33(29):3356-3364.
[6] Wang J, Shi M, Hsia Y, et al. Failure patterns and survival in patients with nasopharyngeal carcinoma treated with intensity modulated radiation in Northwest China: a pilot study[J]. Radiat Oncol,2012,7(1):2-8.
[7] Blanchard P, Lee A, Marguet S, et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis[J]. Lancet Oncol, 2015,16(6):645-655.
[8] Chan AT, Leung SF, Ngan RK, et al. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapyalone in locoregionally advanced nasopharyngeal carcinoma[J]. J Natl Cancer Inst, 2005,97(7):536-539.
[9] Wang D, Zhou J, Zheng J, et al. Predictive value of excision repair cross-complementation group 1 expression in locoregionally advanced nasopharyngeal carcinoma receiving cisplatin-based concurrent chemoradiotherapy[J]. Cancer Biomark, 2018,21(4):875-881.
[10] Jin H, Xie X, Wang H, et al. ERCC1 Cys8092Ala and XRCC1 Arg399Gln polymorphisms predict progression-free survival after curative radiotherapy for nasopharyngeal carcinoma[J]. PLoS One, 2014,9(7):e101256.
[11] Chen C, Wang F, Wang Z, et al. Polymorphisms in ERCC1 C8092A predict progressionfree survival in metastatic/recurrent nasopharyngeal carcinoma treated With cisplatinbased chemotherapy[J]. Cancer Chemother Pharmacol,2013,72(2):315-322.
[12] Ma BB, Hui EP, Wong SC, et al. Multicenter phase II study of gemcitabine and oxaliplatin in advanced nasopharyngeal carcinoma-correlation with excision repair cross-complementing-1 polymorphisms[J]. Ann Oncol, 2009,20(11):1854-1859.
[13] Zhang HP, Zhang D, Xu EC, et al. Relationship between single nucleotide polymorphisms of ERCC1, XRCC1 and efficacy of radiochemotherapy in patients with nasopharyngeal cancer[J]. Journal of Chinese Oncology,2017,23(1):40-44.
[14] Friboulet L, Olaussen KA, Pignon JP, et al. ERCC1 isoform expression and DNA repair in non-small-cell lung cancer[J]. N Engl J Med, 2013,368(12):1101-1110.
[15] Friboulet L, Barrios-Gonzales D, Commo F, et al. Molecular Characteristics of ERCC1-Negative versus ERCC1-Positive Tumors in Resected NSCLC[J]. Clin Cancer Res, 2011,17 (17): 5562-5572.
[16] Friboulet L, Postel-Vinay S, Sourisseau T, et al. ERCC1 function in nuclear excision and interstrand crosslink repair pathways is mediated exclusively by the ERCC1-202 isoform[J]. Cell Cycle, 2013,12(20):3298-3306.
[17] Hui EP, Ma BB, Chan KC, et al. Clinical utility of plasma Epstein-Barr virus DNA and ERCC1 single nucleotide polymorphism in nasopharyngeal carcinoma[J]. Cancer, 2015,121(16):2720-2729.
[18] Lu Y, Huang HX, Kang M, et al.Combined Ki67 and ERCC1 for prognosis in non-keratinizing nasopharyngeal carcinoma underwent chemoradiotherapy[J]. Oncotarget, 2017, 8(51): 88552-88562.
[19] Xu S, Yu Y, Rong J, et al. Expression of BRCA1 and ERCC1 as predictive clinical outcome after radiochemotherapy in patients with locoregionally moderate-advanced nasopharyngeal carcinoma[J]. Oncotarget, 2017,8(19):31355-31367.