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错配修复蛋白(MMR)和KRAS的生物分析——结直肠癌诊断的关键因素

Bioanalysis of MMR and KRAS - a key factor in diagnosis of colorectal cancer.

作者信息

Stefan-van Staden Raluca-Ioana, Bratei Alexandru Adrian, Ilie-Mihai Ruxandra-Maria, Gheorghe Damaris-Cristina, Tuchiu Bianca Maria, Gurzu Simona

机构信息

Laboratory of Electrochemistry and PATLAB, National Institute of Research for Electrochemistry and Condensed Matter 202 Splaiul Independentei Str. 060021 Bucharest-6 Romania

Faculty of Chemical Engineering and Biotechnologies, Politehnica University of Bucharest Bucharest Romania.

出版信息

RSC Adv. 2023 Aug 11;13(34):24086-24092. doi: 10.1039/d3ra04260j. eCollection 2023 Aug 4.

DOI:10.1039/d3ra04260j
PMID:37577090
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10415748/
Abstract

Two miniaturized electrochemical devices were designed for the simultaneous bioanalysis of MMR (MLH1, MSH2, MSH6, PMS2), and of KRAS in whole blood, urine, saliva, and tumoral tissues. The devices comprised besides the electronic part of the potentiostat a combined 3D stochastic microsensor (combined microplatform) with the sensing part based on the modification of graphene decorated with nitrogen, sulfur and boron (NSB-EGR) modified with two types of frutafit: FTEX and FHD. For the assay of MSH2, MSH6, KRAS, and PMS2 higher sensitivities were recorded when the microdevice based on FHD was used, while for the assay of MLH1 the best sensitivity was achieved by using the microdevice based on FTEX. While the limits of quantification for MLH1, MSH2, and PMS2 were not influenced by the modifier, the microdevice based on FHD provided the lowest limit of quantification for KRAS, the microdevice based on FTEX provided the lowest limit of quantification for MSH6. The validation tests performed proved that recoveries of MLH1, MSH2, MSH6, PMS2, and of KRAS in whole blood, urine, saliva, and tumoral tissues higher than 98.50% with RSD (%) values lower than 0.10% were recorded.

摘要

设计了两种小型化电化学装置,用于同时对全血、尿液、唾液和肿瘤组织中的错配修复蛋白(MLH1、MSH2、MSH6、PMS2)和KRAS进行生物分析。这些装置除了包含恒电位仪的电子部分外,还包括一个组合式3D随机微传感器(组合微平台),其传感部分基于用两种类型的弗鲁塔菲特(FTEX和FHD)修饰的氮、硫和硼修饰的石墨烯(NSB-EGR)。在检测MSH2、MSH6、KRAS和PMS2时,使用基于FHD的微型装置记录到更高的灵敏度,而在检测MLH1时,使用基于FTEX的微型装置获得了最佳灵敏度。虽然MLH1、MSH2和PMS2的定量限不受修饰剂的影响,但基于FHD的微型装置对KRAS提供了最低的定量限,基于FTEX的微型装置对MSH6提供了最低的定量限。所进行的验证测试证明,全血、尿液、唾液和肿瘤组织中MLH1、MSH2、MSH6、PMS2和KRAS的回收率高于98.50%,相对标准偏差(RSD)(%)值低于0.10%。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f90f/10415748/c85a8c3eeebd/d3ra04260j-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f90f/10415748/58ef8156b3f4/d3ra04260j-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f90f/10415748/14e2e49c05f9/d3ra04260j-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f90f/10415748/412260ad9aea/d3ra04260j-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f90f/10415748/c85a8c3eeebd/d3ra04260j-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f90f/10415748/58ef8156b3f4/d3ra04260j-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f90f/10415748/14e2e49c05f9/d3ra04260j-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f90f/10415748/412260ad9aea/d3ra04260j-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f90f/10415748/c85a8c3eeebd/d3ra04260j-f3.jpg

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本文引用的文献

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Precision oncology for KRAS-mutant colorectal cancer.KRAS 突变型结直肠癌的精准肿瘤学
Nat Rev Clin Oncol. 2023 Jun;20(6):355-356. doi: 10.1038/s41571-023-00748-z.
2
Enantioanalysis of glutamine-a key factor in establishing the metabolomics process in gastric cancer.对谷氨酰胺的对映体分析——胃癌代谢组学研究过程中的一个关键因素。
Anal Bioanal Chem. 2020 May;412(13):3199-3207. doi: 10.1007/s00216-020-02575-y. Epub 2020 Mar 18.
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Enantioanalysis of tryptophan in whole blood samples using stochastic sensors-A screening test for gastric cancer.
利用随机传感器对手性血液样本中色氨酸的分析 - 胃癌的筛选试验。
Chirality. 2020 Feb;32(2):215-222. doi: 10.1002/chir.23155. Epub 2019 Nov 20.
4
EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome.EPCAM 突变更新:与先天性簇状肠病和林奇综合征相关的变异。
Hum Mutat. 2019 Feb;40(2):142-161. doi: 10.1002/humu.23688. Epub 2018 Nov 29.
5
Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part I-Colorectal Cancer: Microsatellite Instability, Testing, and Clinical Implications.程序性死亡配体-1检测及免疫疗法在微卫星不稳定的结直肠癌中是否有作用?第一部分——结直肠癌:微卫星不稳定、检测及临床意义
Arch Pathol Lab Med. 2018 Jan;142(1):17-25. doi: 10.5858/arpa.2017-0040-RA. Epub 2017 Nov 16.
6
Use of multigene-panel identifies pathogenic variants in several CRC-predisposing genes in patients previously tested for Lynch Syndrome.多基因panel 检测可在先前检测林奇综合征的患者中鉴定出几种 CRC 易患基因的致病性变异。
Clin Genet. 2017 Oct;92(4):405-414. doi: 10.1111/cge.12994. Epub 2017 Mar 22.
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The consensus molecular subtypes of colorectal cancer.结直肠癌的共识分子亚型
Nat Med. 2015 Nov;21(11):1350-6. doi: 10.1038/nm.3967. Epub 2015 Oct 12.
8
American Gastroenterological Association Technical Review on the Diagnosis and Management of Lynch Syndrome.美国胃肠病学会关于林奇综合征诊断与管理的技术评估
Gastroenterology. 2015 Sep;149(3):783-813.e20. doi: 10.1053/j.gastro.2015.07.037. Epub 2015 Jul 27.
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PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.错配修复缺陷肿瘤中的程序性死亡受体-1阻断
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Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on colorectal cancer.林奇综合征遗传评估与管理指南:美国结直肠多学会工作组共识声明。
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