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基于电感耦合等离子体质谱的肿瘤标志物检测
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作者单位
王超群,刘睿,周静,吕弋 1.四川大学分析测试中心四川成都6100642.四川大学化学学院四川成都610064 
基金项目:国家自然科学基金(22074096);四川省科技厅重点项目(19CXRC0047)
中文摘要:癌症是导致死亡的重要原因和提高预期寿命的严重阻碍。研究表明,早期的诊断和治疗是降低死亡率最有效的途径。肿瘤标志物的浓度变化通常与肿瘤发生、肿瘤细胞转移和临床治疗相关,肿瘤标志物检测对癌症的早期诊断,进展监测和预后具有重要的意义。近二十年来,基于电感耦合等离子体质谱(ICP-MS)检测肿瘤标志物的方法引起了研究者的广泛关注。ICP-MS具有分辨率高、灵敏度高、动态范围宽以及可多元素同时检测的优势。结合稳定同位素标记策略,已有许多基于ICP-MS的肿瘤标志物检测方法被报道。该文介绍了几种常见肿瘤标志物及其ICP-MS检测方法,并简要总结了ICP-MS在多组分生物标志物同时检测中的应用。
中文关键词:金属稳定同位素  生物分析  电感耦合等离子体质谱  肿瘤标志物  综述
 
Research on Tumor Marker Determination Methods Based on Inductively Coupled Plasma Mass Spectrometry
Abstract:Cancer is a leading cause of death and a severe impediment to increasing life expectancy.According to Global Cancer Statistics 2020,there are an estimation of 19.3 million new cancer cases and 10 million cancer deaths worldwide in 2020.Early diagnosis and treatment are crucial to reducing cancer mortality.Tumor markers are the metabolic and immune molecules produced by tumor cells or tumor-related normal tissues.The concentration of tumor marker will change abnormally with the tumor occurrence,metastasis and treatment.Tumor marker detection is of great significance for cancer's early diagnosis,progress monitoring,and prognosis.Carcinoembryonic antigen(CEA) is a broad-spectrum tumor marker related to colorectal cancer,pancreatic cancer,liver cancer,lung cancer,breast cancer and ovarian cancer.Prostate-specific antigen(PSA) monitoring in serum effectively diagnoses whether prostate cancer has recurred after surgery.Ultrasonography combined with alpha-fetoprotein(AFP) detection could effectively screen and diagnose hepatocellular carcinoma(HCC) for high-risk patients.But most importantly,inductively coupled plasma mass spectrometry(ICP-MS) is an analytical method with high resolution,high sensitivity,wide dynamic range(9 orders of magnitude) and multi-element simultaneous detection.In the past two decades,ICP-MS methods based on stable isotope labels have been widely used to detect metal ions,nucleic acids,peptides,proteins,enzymes,small molecules and single cells.Currently,ICP-MS methods for tumor markers detection have also been widely reported.In this review,according to distinct interactions,ICP-MS methods are divided into two types:immunoassay methods and nucleic acid-based methods.The construction and application of each are discussed in the subsequent section.In the third part,common tumor markers and related cancer types are summarized in a table.CEA,PSA,AFP,and their ICP-MS detection methods are described in detail,along with the separation method of excess tags and the signal amplification mechanism of nanoparticle tags are discussed.Besides,only one tumor marker detection may get a false-positive result.Multiple detection could effectively reduce the false positive rate and improve the specificity of diagnosis.This approach's advantage lies in reducing sample consumption,shortening experiment time,and improving diagnostic accuracy.Thus,multiple detection has attracted widespread attention.Combined with laser ablation inductively coupled plasma mass spectrometry(LA-ICP-MS) and flow cytometry mass spectrometry,it is possible to simultaneously determine multiple proteins on a single microarray spot,cell,and cancer tissue.Multiple biomarkers detection based on ICP-MS is briefly described,and the challenge of constructing multiple detection methods is also discussed in this review.Finally,limitations of ICP-MS detection methods based on element labeling are discussed.Anticipated developments in ICP-MS detection are proposed,including:①Development of new strategies,②Combination with other technologies such as big data analysis,③Transformation of laboratory research results into clinical application technologies.
Key Words:metal stable isotope  bioassay  inductively coupled plasma mass spectrometry  tumor marker  review
引用本文:王超群,刘睿,周静,吕弋.基于电感耦合等离子体质谱的肿瘤标志物检测[J].分析测试学报,2021,40(6):843-850.
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