基于质谱的高通量蛋白质组学技术探索肿瘤蛋白标志物的研究进展

Research progress on tumor protein biomarkers using high-throughput proteomics based on mass spectrometry

蛋白质组学研究虽已开展20余年,早期研究基于Western blot技术,后来采用质谱技术鉴定蛋白质。但最初质谱技术的测序深度和鉴定蛋白质数量有限,使蛋白质组学研究遇到瓶颈。近年来,随着质谱技术的飞速发展,实现了高通量的蛋白质组学鉴定,从此蛋白质组学研究进入新时代。目前,高通量蛋白质组学技术在肿瘤领域的应用主要包括揭示肿瘤发生发展机制、寻找特异性生物标志物、阐明耐药性产生机制和发现新治疗靶点等。肿瘤的早期发现和诊断有助于及时地进行医疗干预,从而大幅提高患者的生存率及生存质量。国内外研究已发现了很多候选肿瘤生物标志物,但仅极少数应用于临床。因此,仅针对探索肿瘤特异性生物标志物,本文选取并分析高通量蛋白质组学技术应用较为广泛深入、且发病率/死亡率较高的肺癌、乳腺癌、结直肠癌和肝癌4种肿瘤类型。在不同肿瘤类型中筛选发表期刊影响因子较高、经扩大样本量验证或功能验证、证据较强的研究。介绍基于质谱的高通量蛋白质组学技术和常用标本类型,重点综述在上述4种高发癌症中,基于该技术发现的可能用于早期诊断、预测预后、靶向治疗的蛋白质标志物,旨在为实现肿瘤精准诊疗提供新的理论依据。

Proteomics research has been performed for more than 20 years.Early research was based on simple Western blot technology,and later,mass spectrometry was used to identify proteins.However,the limited sequencing depth and the number of identified proteins in initial mass spectrometry technology have caused bottlenecks in proteomics research.In recent years,with the rapid development of mass spectrometry technology,high-throughput proteomics identification has been achieved,and proteomics research has entered a new era.At present,the application of high-throughput proteomics technology in the field of cancer mainly includes revealing the mechanism of tumorigenesis and development,searching for specific biomarkers,elucidating the mechanism of drug resistance,and identifying new therapeutic targets.Early detection and diagnosis of tumors are helpful for timely medical intervention,greatly improving the survival rate and quality of life.Recently,several candidate tumor biomarkers have been identified,but only a few have been used clinically.Here,aiming to explore tumor-specific biomarkers,we selected four high morbidity/mortality rate tumors with extensive application of high-throughput proteomics technology,such as lung,breast,colorectal,and liver cancer.We screened recently published studies from journals with high impact factors,evaluated by their expanded sample size or functional verification,and strong evidence in different tumor types.This article first briefly introduces mass spectrometry-based high-throughput proteomics technology and commonly used specimen types,and then focuses on reviewing the protein markers that may be used for early diagnosis,prognosis,and targeted therapy in the above four high-incidence cancers,aiming to provide a new theoretical basis for accurate diagnosis and treatment of tumors.