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癌症耐药性的蛋白质基因组学研究:迈向生物标志物发现与靶点鉴定

Proteogenomic studies on cancer drug resistance: towards biomarker discovery and target identification.

作者信息

Fu Shuyue, Liu Xiang, Luo Maochao, Xie Ke, Nice Edouard C, Zhang Haiyuan, Huang Canhua

机构信息

a State Key Laboratory of Biotherapy and Cancer Center , West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , P.R. China.

b Department of Pathology , Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital , Chengdu , P.R. China.

出版信息

Expert Rev Proteomics. 2017 Apr;14(4):351-362. doi: 10.1080/14789450.2017.1299006. Epub 2017 Mar 6.

Abstract

Chemoresistance is a major obstacle for current cancer treatment. Proteogenomics is a powerful multi-omics research field that uses customized protein sequence databases generated by genomic and transcriptomic information to identify novel genes (e.g. noncoding, mutation and fusion genes) from mass spectrometry-based proteomic data. By identifying aberrations that are differentially expressed between tumor and normal pairs, this approach can also be applied to validate protein variants in cancer, which may reveal the response to drug treatment. Areas covered: In this review, we will present recent advances in proteogenomic investigations of cancer drug resistance with an emphasis on integrative proteogenomic pipelines and the biomarker discovery which contributes to achieving the goal of using precision/personalized medicine for cancer treatment. Expert commentary: The discovery and comprehensive understanding of potential biomarkers help identify the cohort of patients who may benefit from particular treatments, and will assist real-time clinical decision-making to maximize therapeutic efficacy and minimize adverse effects. With the development of MS-based proteomics and NGS-based sequencing, a growing number of proteogenomic tools are being developed specifically to investigate cancer drug resistance.

摘要

化疗耐药是当前癌症治疗的主要障碍。蛋白质基因组学是一个强大的多组学研究领域,它利用由基因组和转录组信息生成的定制蛋白质序列数据库,从基于质谱的蛋白质组学数据中识别新基因(如非编码基因、突变基因和融合基因)。通过识别肿瘤与正常样本之间差异表达的畸变,这种方法也可用于验证癌症中的蛋白质变体,这可能揭示对药物治疗的反应。涵盖领域:在本综述中,我们将介绍癌症耐药性蛋白质基因组学研究的最新进展,重点是综合蛋白质基因组学流程以及有助于实现精准/个性化癌症治疗目标的生物标志物发现。专家评论:潜在生物标志物的发现和全面理解有助于识别可能从特定治疗中获益的患者群体,并将协助实时临床决策,以最大限度地提高治疗效果并最小化不良反应。随着基于质谱的蛋白质组学和基于二代测序(NGS)的测序技术的发展,越来越多专门用于研究癌症耐药性的蛋白质基因组学工具正在被开发出来。

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