高通量转录组测序初步研究结肠直肠癌新辅助治疗敏感性

doi:10.16139/j.1007-9610.2018.01.015

外科理论与实践 ›› 2018, Vol. 23 ›› Issue (01): 67-71.doi: 10.16139/j.1007-9610.2018.01.015

高通量转录组测序初步研究结肠直肠癌新辅助治疗敏感性

陈献则, 程兮^*, 吴浩旋, 张弢, 季晓频, 赵任

上海交通大学医学院附属瑞金医院外科上海消化外科研究所,上海 200025

收稿日期:2017-08-07 出版日期:2018-01-25 发布日期:2020-07-25
通讯作者: 季晓频,E-mail: surgeonjee@hotmail.com;赵任,E-mail: zhaorensurgeon@aliyun.com
作者简介:*共同第一作者
基金资助:
上海市科委项目（14411950504）; 上海申康中心市级医院临床技能与临床创新能力3年行动计划（16CR3064B）; 上海交通大学医学院博士研究生创新基金(BXJ201709)

Preliminary research on colorectal cancer neoadjuvant therapy sensitivity through high-throughput transcriptome sequence

CHEN Xianze, CHENG Xi, WU Haoxuan, ZHANG Tao, JI Xiaopin, ZHAO Ren

Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received:2017-08-07 Online:2018-01-25 Published:2020-07-25

摘要/Abstract

摘要： 目的采用高通量转录组测序技术,通过生物信息学手段,初步筛选并鉴定结肠直肠癌病人术前新辅助治疗效果相关基因,并进行差异表达分析,为进一步阐明结肠直肠癌新辅助治疗敏感性的分子机制提供基础。方法 22例接受标准术前新辅助治疗的结肠直肠癌病人,根据肿瘤消退评级分为敏感组9例,不敏感组13例。提取肿瘤组织RNA,构建转录组文库,采用高通量测序平台进行测序。结合生物信息学等相关手段,筛除错误发生率（<0.05）的基因后对比组装,对得到的转录组样本进行分类和注释。对差异表达基因特征进行分析。结果初步建立结肠直肠癌新辅助治疗敏感性基因数据库。从22例转录组标本中,发现89个基因表达出现显著上调,112个基因出现显著下调。结论高通量测序分析提示,这些基因表达变化可能与结肠直肠癌新辅助治疗敏感性密切相关。

关键词: 结肠直肠癌, 新辅助治疗, 治疗敏感性, 转录组测序

Abstract: Objective To screen and identify the genes associated with sensitivity of neoadjuvant therapy for the patients with colorectal cancer through high-throughput transcriptome sequence technology and bioinformatics tools by analysis of the genes which expressed differently. Methods RNA was extracted from the tumor tissue of 22 patients with co-lorectal cancer who received standard neoadjuvant therapy before operation. Nine cases were divided as sensitive group and 11 cases as non-sensitive group based on tumor regression grading. Strand libraries were constructed for high-throughput sequencing. The genes filtered the false discovery rate(<0.05) were mapped to the reference genome, and assembled. The obtained transcripts were classified and annotated and the characteristics of gene were analyzed. Results The gene database associated with neoadjuvant therapy for colorectal cancer was built preliminarily. From 22 patients with colorectal cancer tissues, 89 genes were found up-regulated significantly and 112 genes down-regulated. Conclusions The genes related to the sensitivity of colorectal cancer neoadjuvant therapy were identified in this study using high-throughput transcriptome sequence.

Key words: Colorectal Cancer, Neoadjuvant therapy, Therapy sensitivity, Transcriptome sequencing

中图分类号:

陈献则, 程兮, 吴浩旋, 张弢, 季晓频, 赵任. 高通量转录组测序初步研究结肠直肠癌新辅助治疗敏感性[J]. 外科理论与实践, 2018, 23(01): 67-71.

CHEN Xianze, CHENG Xi, WU Haoxuan, ZHANG Tao, JI Xiaopin, ZHAO Ren. Preliminary research on colorectal cancer neoadjuvant therapy sensitivity through high-throughput transcriptome sequence[J]. Journal of Surgery Concepts & Practice, 2018, 23(01): 67-71.

参考文献

[1] 赵任, 蒋奕玫. 直肠癌外科手术治疗进展[J]. 外科理论与实践,2016,16(6):468-471.
[2] Kuebler JP, Wieand HS, O′Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage Ⅱ and Ⅲ colon cancer: results from NSABP C-07[J]. J Clin Oncol,2007,25(16):2198-2204.
[3] Haller DG, Tabernero J, Maroun J, et al.Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stageⅢ colon cancer[J]. J Clin Oncol,2011,29(11):1465-1471.
[4] McGee MF, Benson AB 3rd. Adjuvant chemotherapy for stageⅡ colon cancer: everyone still needs a tailor[J]. Ann Surg Oncol,2014,21(16):1765-1767.
[5] Teufel A, Gerken M, Hartl J, et al.Benefit of adjuvant chemotherapy in patients with T4 UICC Ⅱ colon cancer[J]. BMC Cancer,2015,15(8):419.
[6] Gunderson LL, Jessup JM, Sargent DJ, et al.Revised TN categorization for colon cancer based on national survival outcomes data[J]. J Clin Oncol,2010,28(2):264-271.
[7] 顾晋, 陈鹏举. 胃肠外科医师应重视结直肠癌的辅助化疗[J]. 中华胃肠外科杂志,2015,18(10):974-978.
[8] 孙艳武, 池畔, 徐本华, 等. 直肠癌新辅助放化疗后病理完全缓解预测因素分析[J]. 中华胃肠外科杂志,2014,17(6):556-560.
[9] Kapranov P, Cheng J, Dike S, et al.RNA maps reveal new RNA classes and a possible function for pervasive transcription[J]. Science,2007,316(5830):1484-1488.
[10] 孙凯, 黄晓卉, 甄茂川, 等. 应用液相芯片分析肝细胞癌及癌旁组织小分子RNA表达谱差异[J]. 中华实验外科杂志,2006,23(8):945-947.
[11] 李智勇, 林维文, 官国先, 等. 新辅助放化疗对mrT3期低位直肠癌患者不同浸润深度远期疗效的影响[J]. 中国肿瘤临床,2015,13(5):377-379.
[12] 戴朝六, 徐峰. 个体化治疗直肠癌同时性肝转移[J]. 中华消化外科杂志,2014,13(3):175-179.
[13] Maas M, Nelemans PJ, Valentini V, et al.Adjuvant chemotherapy in rectal cancer: defining subgroups who may benefit after neoadjuvant chemoradiation and resection a pooled analysis of 3,313 patients[J]. Int J Cancer,2015,137(1):212-220.
[14] Collette L, Bosset JF, den Dulk M, et al. Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group[J]. J Clin Oncol,2007,25(28):4379-4386.
[15] Hong YS, Nam BH, Kim KP, et al.Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leuco-vorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy(ADORE): an open-label, multicentre, phase 2, randomised controlled trial[J]. Lancet Oncol,2014,15(11):1245-1253.
[16] Zorcolo L, Rosman AS, Restivo A, et al.Complete pathologic response after combined modality treatment for rectal cancer and long-term survival: a meta-analysis[J]. Ann Surg Oncol,2012,19(9):2822-2832.
[17] Bujko K, Glynne-Jones R, Bujko M.Does adjuvant fluoropyrimidine-based chemotherapy provide a benefit for patients with resected rectal cancer who have already received neoadjuvant radiochemotherapy? A systematic review of randomised trials[J]. Ann Oncol,2010,21(9):1743-1750.
[18] Yothers G, O'Connell MJ, Allegra CJ, et al. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses[J]. J Clin Oncol,2011,29(28):3768-3774.
[19] Colas E, Muinelo-Romay L, Alonso-Alconada L, et al.ETV5 cooperates with LPP as a sensor of extracellular signals and promotes EMT in endometrial carcinomas[J]. Oncogene,2012,31(45):4778-4788.
[20] Bao Y, Peng W, Verbitsky A, et al.Human coxsackie adenovirus receptor(CAR) expression in transgenic mouse prostate tumors enhances adenoviral delivery of genes[J]. Prostate,2005,64(4):401-407.

高通量转录组测序初步研究结肠直肠癌新辅助治疗敏感性

Preliminary research on colorectal cancer neoadjuvant therapy sensitivity through high-throughput transcriptome sequence

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	许梓枫, 宗雅萍, 陆爱国. 局部进展期结肠癌病人的新辅助治疗[J]. 外科理论与实践, 2022, 27(3): 266-270.
[2]	陈小松, 沈坤炜, 李宏为. 早期可手术乳腺癌的诊治现状与展望[J]. 外科理论与实践, 2022, 27(05): 385-386.
[3]	张吉祥, 谢智华, 综述, 李炜, 姜小清, 审校. 肝内胆管癌的分型和外科治疗热点[J]. 外科理论与实践, 2022, 27(05): 478-482.
[4]	郭杨, 郭天安, 徐烨. 直肠癌新辅助化疗的研究进展[J]. 外科理论与实践, 2022, 27(04): 370-374.
[5]	包全, 邢宝才. 复杂双叶多发性结肠直肠癌肝转移外科治疗策略[J]. 外科理论与实践, 2022, 27(02): 128-130.
[6]	黄乃思, 陈嘉莹, 嵇庆海, 王宇. 靶向药物时代局部晚期甲状腺癌的新辅助治疗[J]. 外科理论与实践, 2021, 26(6): 493-496.
[7]	刘诗光, 赵敬坤, 陆爱国, 毛志海. 趋化因子CXCL5和程序性死亡配体 1在结肠直肠癌组织的表达与病人预后的关系[J]. 外科理论与实践, 2021, 26(6): 543-549.
[8]	张华, 陆炜, 杨承翌, 项明洁. 血清人衰老关键蛋白1检测对结肠直肠癌的诊断和预后价值[J]. 诊断学理论与实践, 2021, 20(05): 462-465.
[9]	杨盈赤, 宋建宁, 张忠涛. 中国腹腔镜结肠直肠手术的回顾与展望——基于手术病例登记研究和数据库建立的思考[J]. 外科理论与实践, 2021, 26(04): 277-280.
[10]	顾晋. 局部晚期结肠直肠癌治疗和联合脏器切除[J]. 外科理论与实践, 2021, 26(04): 290-296.
[11]	吴春晓, 龚杨明, 顾凯, 庞怡, 鲍萍萍, 王春芳, 施亮, 向詠梅, 窦剑明, 付晨, 施燕. 2016年上海市结肠直肠癌发病和死亡情况与2002—2016年间的变化趋势分析[J]. 外科理论与实践, 2021, 26(04): 325-335.
[12]	蔡三军. 结肠直肠癌诊治的思考[J]. 外科理论与实践, 2021, 26(04): 297-299.
[13]	张弢, 叶枫, 赵任. 结肠直肠癌的微创手术——在工具和价值间的不断平衡优化[J]. 外科理论与实践, 2021, 26(04): 300-304.
[14]	杨飖, 傅传刚. NOSES在结肠直肠癌手术中的应用现状与展望[J]. 外科理论与实践, 2021, 26(04): 305-311.
[15]	王常刚, 刘坤, 冯浩然, 蒋奕玫, 施毅卿, 陈献则, 宋子甲, 李军, 李佑, 蔡东莉, 赵任. 结肠直肠癌B7S1表达与免疫浸润的关系[J]. 外科理论与实践, 2021, 26(04): 336-342.