结直肠癌术后辅助卡培他滨为基础化疗方案的临床疗效及相关药物基因组学分析

刘世举; 张慧俭; 王金榜; 杨会举; 张新春; 刘翔; 刘佃温

doi:10.3969/j.issn.1000-8179.2018.17.623

结直肠癌术后辅助卡培他滨为基础化疗方案的临床疗效及相关药物基因组学分析

doi: 10.3969/j.issn.1000-8179.2018.17.623

刘世举^①,,
张慧俭^②,
王金榜^③,
杨会举^①,
张新春^①,
刘翔^①,
刘佃温^①, ,

①.
河南中医药大学第三附属医院肛肠外科（郑州市450000）
②.
河南中医药大学针灸推拿学院（郑州市450000）
③.
河南省肿瘤医院普外科（郑州市450000）

基金项目:

河南省科技厅科技攻关项目 162102310109

河南省教育厅基础研究项目 15A360006

详细信息

作者简介:
刘世举专业方向为中西医结合防治肛肠疾病。E-mail：Liusj120@126.com

通讯作者:
刘佃温 Liudianwen6207@126.com

计量
- 文章访问数: 61
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- 被引次数: 0
出版历程
- 收稿日期: 2018-06-10
- 修回日期: 2018-09-04
- 刊出日期: 2018-09-15

Efficacy of capecitabine-based adjuvant chemotherapy in colorectal cancer patients after radical resection and the corresponding pharmacogenomics analysis

Liu Shiju^{①
,},
Zhang Huijian^②,
Wang Jinbang^③,
Yang Huiju^①,
Zhang Xinchun^①,
Liu Xiang^①,
Liu Dianwen^{①
, ,}

①.
Department of Anus and Intestine Surgery, The Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China
②.
Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China
③.
Tumor Hospital of Henan Province, Zhengzhou 450000, China

Funds:

Science and Technology Breakthrough Project of Science and Technology Department of Henan Province 162102310109

Basic Research Project of Education Department of Henan Province 15A360006

More Information

Corresponding author: Dianwen Liu, E-mail:Liudianwen6207@126.com

摘要

摘要: 目的本研究旨在探讨结直肠癌（colorectal cancer，CRC）术后辅助卡培他滨为基础化疗方案的疗效及相关药物基因组学分析。方法回顾性分析2010年1月至2017年6月河南中医药大学第三附属医院收治术后接受辅助化疗的CRC患者215例。收集外周血提取DNA用来进行胞苷脱氨酶（cytidine deaminase，CDD）多态性位点基因分型。另外，收集85例患者的化疗前外周血单核细胞（peripheral blood mononuclear cell，PBMC）提取RNA对CDD的mRNA表达水平进行测定。结果 215例患者具有良好的疗效。药物基因组学分析方面，发现CDD基因启动子区域的多态性位点-451C>A和疗效相关，该位点GA/AA和GG基因型患者的3年无疾病生存率（disease-free survival，DFS）分别为81.03%和62.42%，差异具有统计学意义（P=0.002）。两种基因型患者的5年总生存率（overall survival，OS）分别为72.41%和53.50%，差异具有统计学意义（P=0.016）。在85例患者外周血单核细胞的mRNA表达分析中发现，携带A等位基因的患者相对于GG型患者，外周血单核细胞中CDD的mRNA表达明显较高，差异具有统计学意义（P < 0.001）。结论卡培他滨为基础的化疗方案具有良好的治疗效果。CDD基因-451C>A位点可能通过影响该基因mRNA的表达使CRC患者从卡培他滨的治疗当中获益。
- 结直肠癌 /
- 胞苷脱氨酶 /
- 多态性 /
- 疗效
Abstract: Objective To investigate the clinical outcomes of colorectal cancer (CRC) patients who received capecitabine-based adjuvant chemotherapy after radical resection and the corresponding pharmacogenomics analysis. Methods In The Third Affiliated Hospital of Henan University of Traditional Chinese Medicine from Jannary 2010 to June 2017. A total of 215 patients with CRC who received capecitabine-based adjuvant chemotherapy were included in this study. Peripheral blood of the CRC patients was collected for DNA extraction and genotyping of polymorphisms for CDD. Additionally, pretreated peripheral blood mononuclear cells (PBMC) of 85 CRC patients were collected for cytidine deaminase (CDD) mRNA expression analysis. Association analysis of CDD mRNA expression and polymorphisms was performed. Results Clinical outcomes of the 215 patients were favorable. In terms of the corresponding pharmacogenomics analysis, of the polymorphisms studied, -451C>A was found to be of clinical significance. The survival analysis of patients with different genotypes revealed that the 3-year disease-free survival (DFS) of patients with the GA/AA genotype and the GG genotype was 81.03% and 62.42%, respectively, indicating a statistically significant difference (P=0.002). In terms of overall survival (OS), the 5- year OS of patients with the two genotypes was 72.41% and 53.50%, respectively, which also indicated a statistically significant difference (P=0.016). Additionally, analysis of mRNA expression in 85 PBMC samples showed that CDD mRNA expression in patients with GA or AA genotypes was significantly higher than in those with the GG genotype (P < 0.001). Conclusions The clinical outcomes of postoperative CRC patients who received capecitabine-based adjuvant chemotherapy were favorable. CDD mRNA expression may be affected by the -451C>A polymorphism, making CRC patients get benefits from capecitabine treatment.
- colorectal cancer /
- cytidine deaminase /
- polymorphism /
- efficacy

HTML全文

图 1 215例CRC患者中CDD基因-451C>A位点不同基因型患者的DFS曲线

下载: 全尺寸图片幻灯片

图 2 215例CRC患者中CDD基因-451C>A位点不同基因型患者的OS曲线

下载: 全尺寸图片幻灯片

图 3 CDD基因-451C>A位点不同基因型患者的相对CDD mRNA表达

下载: 全尺寸图片幻灯片

表 1 215例CRC患者的基线临床资料及-451C>A位点基因型的基线临床资料对比 n（%）

表 2 影响DFS的基线临床资料以及多态性位点的多变量Cox回归分析

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