• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

遗传多态性和肿瘤突变特征对晚期结直肠癌患者生存的影响：一项探索性研究。

Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study.

机构信息

Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology (DOBC), Faculty of Medicine, University of Chile, Santiago 8350499, Chile.

Latin American Network for Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago 8350499, Chile.

出版信息

Curr Oncol. 2024 Jan 3;31(1):274-295. doi: 10.3390/curroncol31010018.

DOI:10.3390/curroncol31010018
PMID:38248103
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10814806/
Abstract

Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug (FOLFOX, CapeOX). Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic response, considering their interaction with oncogene mutations (, , , , ). In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, , , and polymorphisms are independent indicators of poor prognosis, irrespective of oncogene mutations. wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to -mutated cell lines. In conclusion, the genetic polymorphisms , , and may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of oncogene mutations.

摘要

结直肠癌是一种常见疾病，无论是在智利还是在全球范围内。最广泛使用的化疗方案是基于氟尿嘧啶（5FU）作为基础药物（FOLFOX、CapeOX）。遗传多态性已成为化疗反应的潜在预测生物标志物，但缺乏确凿的证据。本研究旨在探讨与基于 5FU 的化疗相关的遗传变异体在治疗反应中的作用，同时考虑它们与致癌基因突变（、、、、）的相互作用。在一个由 63 名转移性结直肠癌患者组成的回顾性队列中，多变量分析显示，肝转移、、、和 多态性是不良预后的独立指标，与致癌基因突变无关。野生型状态和高风险药物代谢多态性与智利队列中的不良预后相关。此外，药物敏感性基因组学（GDSC）项目的研究结果表明，BRAF 野生型细胞系的 5-FU 的 IC50 值高于 - 突变细胞系。总之，无论致癌基因突变如何，遗传多态性、和 可能成为预测接受氟尿嘧啶化疗的患者预后不良的有用生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/2702d9b452c3/curroncol-31-00018-g008a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/53796ef2246e/curroncol-31-00018-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/4c5822b49c20/curroncol-31-00018-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/31cbca61ddb2/curroncol-31-00018-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/76cc5fb7f3fc/curroncol-31-00018-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/3e0ee21f8c7b/curroncol-31-00018-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/7148e5458272/curroncol-31-00018-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/9fad8b3dff8b/curroncol-31-00018-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/2702d9b452c3/curroncol-31-00018-g008a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/53796ef2246e/curroncol-31-00018-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/4c5822b49c20/curroncol-31-00018-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/31cbca61ddb2/curroncol-31-00018-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/76cc5fb7f3fc/curroncol-31-00018-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/3e0ee21f8c7b/curroncol-31-00018-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/7148e5458272/curroncol-31-00018-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/9fad8b3dff8b/curroncol-31-00018-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d598/10814806/2702d9b452c3/curroncol-31-00018-g008a.jpg

相似文献

1
Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study.遗传多态性和肿瘤突变特征对晚期结直肠癌患者生存的影响：一项探索性研究。
Curr Oncol. 2024 Jan 3;31(1):274-295. doi: 10.3390/curroncol31010018.
2
Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.KRAS、BRAF、NRAS 和 PIK3CA 基因突变对西妥昔单抗联合化疗治疗化疗耐药转移性结直肠癌疗效的影响：一项回顾性联盟分析。
Lancet Oncol. 2010 Aug;11(8):753-62. doi: 10.1016/S1470-2045(10)70130-3. Epub 2010 Jul 8.
3
Clinicopathologic features and treatment efficacy of Chinese patients with BRAF-mutated metastatic colorectal cancer: a retrospective observational study.BRAF 突变型转移性结直肠癌中国患者的临床病理特征及治疗疗效：一项回顾性观察研究
Chin J Cancer. 2017 Oct 16;36(1):81. doi: 10.1186/s40880-017-0247-y.
4
Retrospective study of RAS/PIK3CA/BRAF tumor mutations as predictors of response to first-line chemotherapy with bevacizumab in metastatic colorectal cancer patients.RAS/PIK3CA/BRAF肿瘤突变作为转移性结直肠癌患者一线贝伐单抗化疗反应预测指标的回顾性研究。
BMC Cancer. 2017 Jan 9;17(1):38. doi: 10.1186/s12885-016-2994-6.
5
Role of NRAS mutations as prognostic and predictive markers in metastatic colorectal cancer.NRAS 基因突变作为转移性结直肠癌的预后和预测标志物的作用。
Int J Cancer. 2015 Jan 1;136(1):83-90. doi: 10.1002/ijc.28955. Epub 2014 May 28.
6
KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial.晚期结直肠癌中的KRAS和BRAF突变与预后不良相关，但不排除从奥沙利铂或伊立替康治疗中获益：MRC FOCUS试验结果
J Clin Oncol. 2009 Dec 10;27(35):5931-7. doi: 10.1200/JCO.2009.22.4295. Epub 2009 Nov 2.
7
Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial.超高选择性转移性结直肠癌患者帕尼单抗联合 FOLFIRI 治疗的 KRAS、NRAS、BRAF 和 PIK3CA 高敏基因分型的 II 期研究：ULTRA 试验。
Ann Oncol. 2019 May 1;30(5):796-803. doi: 10.1093/annonc/mdz082.
8
and Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study.并发性结直肠癌标准化学疗法反应的预后和预测生物标志物：单机构研究。
Cells. 2020 Jan 15;9(1):219. doi: 10.3390/cells9010219.
9
Lack of KRAS, NRAS, BRAF and TP53 mutations improves outcome of elderly metastatic colorectal cancer patients treated with cetuximab, oxaliplatin and UFT.KRAS、NRAS、BRAF 和 TP53 基因突变缺失可改善老年转移性结直肠癌患者接受西妥昔单抗、奥沙利铂和 UFT 治疗的预后。
Target Oncol. 2014 Jun;9(2):155-62. doi: 10.1007/s11523-013-0283-8. Epub 2013 Jul 3.
10
KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer.结直肠癌原发肿瘤和 FOLFOX 治疗后转移病灶中的 KRAS 突变。
Br J Cancer. 2012 Jul 10;107(2):340-4. doi: 10.1038/bjc.2012.218. Epub 2012 May 22.

引用本文的文献

1
Understanding microRNA-Mediated Chemoresistance in Colorectal Cancer Treatment.了解微小RNA介导的结直肠癌治疗中的化疗耐药性。
Int J Mol Sci. 2025 Jan 29;26(3):1168. doi: 10.3390/ijms26031168.
2
Can Asiatic Acid from Be a Potential Remedy in Cancer Therapy?-A Review.来自的齐墩果酸能否成为癌症治疗的潜在疗法？——综述
Cancers (Basel). 2024 Mar 28;16(7):1317. doi: 10.3390/cancers16071317.

本文引用的文献

1
genotyping and predicting fluoropyrimidine toxicity: where do we stand?基因分型与氟嘧啶类药物毒性预测：我们目前处于什么位置？
Pharmacogenomics. 2023 Jan;24(2):93-106. doi: 10.2217/pgs-2022-0135. Epub 2023 Jan 13.
2
Genotype-based chemotherapy for patients with gastrointestinal tumors: focus on oxaliplatin, irinotecan, and fluoropyrimidines.基于基因型的胃肠肿瘤化疗：重点关注奥沙利铂、伊立替康和氟嘧啶类药物。
Drug Metab Pers Ther. 2021 Nov 30;37(3):223-228. doi: 10.1515/dmpt-2021-0162. eCollection 2022 Sep 1.
3
Presence of Concurrent Mutations Is Necessary to Predict Poor Outcomes within the Mutated Subgroup of Metastatic Colorectal Cancer.
同时存在突变对于预测转移性结直肠癌突变亚组的不良预后是必要的。
Cancers (Basel). 2022 Jul 27;14(15):3644. doi: 10.3390/cancers14153644.
4
Investigation of , and polymorphisms on 5-fluorouracil related toxicities in colorectal cancer.探讨 5-氟尿嘧啶相关毒性的 、 和 多态性在结直肠癌中的作用。
Per Med. 2022 Sep;19(5):435-444. doi: 10.2217/pme-2021-0047. Epub 2022 Jul 26.
5
Sotorasib for previously treated colorectal cancers with KRAS mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial.索托拉西布治疗 KRAS 突变的既往治疗过的结直肠癌（CodeBreaK100）：一项单臂、2 期试验的预先指定分析。
Lancet Oncol. 2022 Jan;23(1):115-124. doi: 10.1016/S1470-2045(21)00605-7. Epub 2021 Dec 15.
6
Genotyping in Patients Who Have Planned Cancer Treatment With Fluoropyrimidines: A Health Technology Assessment.计划接受氟嘧啶类药物癌症治疗的患者的基因分型：一项卫生技术评估。
Ont Health Technol Assess Ser. 2021 Aug 12;21(14):1-186. eCollection 2021.
7
C677T and A1298C MTHFR gene polymorphisms and response to fluoropyrimidine-based chemotherapy in Mestizo patients with metastatic colorectal cancer.C677T和A1298C亚甲基四氢叶酸还原酶（MTHFR）基因多态性与拉丁裔转移性结直肠癌患者对氟嘧啶类化疗的反应
Pharmacogenet Genomics. 2021 Dec 1;31(9):191-199. doi: 10.1097/FPC.0000000000000440.
8
Role of Glutathione in Cancer: From Mechanisms to Therapies.谷胱甘肽在癌症中的作用：从机制到治疗。
Biomolecules. 2020 Oct 9;10(10):1429. doi: 10.3390/biom10101429.
9
Prognostic impact of cancer stem cell markers and in colorectal cancer.癌症干细胞标志物在结直肠癌中的预后影响
Am J Transl Res. 2020 Sep 15;12(9):5797-5807. eCollection 2020.
10
Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines.荷兰药物遗传学工作组（DPWG）关于 DPYD 和氟嘧啶类药物基因-药物相互作用的指南。
Eur J Hum Genet. 2020 Apr;28(4):508-517. doi: 10.1038/s41431-019-0540-0. Epub 2019 Nov 19.