Differential Proteomic Analysis of Human Saliva using Tandem Mass Tags Quantification for Gastric Cancer Detection.
Differential Proteomic Analysis of Human Saliva using Tandem Mass Tags Quantification for Gastric Cancer Detection.
复制标题
使用串联质量标签定量对人类唾液进行差异蛋白质组分析以检测胃癌。
DOI：
10.1038/srep22165
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发表时间：
2016-02-25
影响因子：
4.6
通讯作者：
Wong DT
中科院分区：
文献类型：
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作者：
Xiao H;Zhang Y;Kim Y;Kim S;Kim JJ;Kim KM;Yoshizawa J;Fan LY;Cao CX;Wong DT
迫切需要新型生物标志物和非侵入性诊断方法来筛查胃癌，以降低其高死亡率。我们采用定量蛋白质组学方法从人唾液中开发用于检测胃癌的区分性生物标志物特征。应用TMT技术对胃癌患者和对照组唾液蛋白质进行分析比较。经定量分析，共鉴定出500多个蛋白质，其中48个蛋白质在正常对照组和胃癌患者组中表达差异显著（p < 0.05），其中7个蛋白质表达上调，41个蛋白质表达下调。选择5种蛋白质通过ELISA进行初步验证，并成功验证了3种，即半胱氨酸蛋白酶抑制剂B（CSTB）、磷酸丙糖异构酶（TPI 1）和恶性脑肿瘤中缺失的1蛋白（DMBT 1）。三种蛋白质对胃癌患者和正常对照组的鉴别诊断有显著性差异（p < 0.05）。三种生物标志物联合检测胃癌的敏感性和特异性分别为85%和80%，准确性为0.93。本研究为唾液生物标志物在胃癌无创检测中的应用提供了理论依据。在大规模验证后，将这些生物标志物转化为适用的临床测试是非常令人鼓舞的。
Novel biomarkers and non-invasive diagnostic methods are urgently needed for the screening of gastric cancer to reduce its high mortality. We employed quantitative proteomics approach to develop discriminatory biomarker signatures from human saliva for the detection of gastric cancer. Salivary proteins were analyzed and compared between gastric cancer patients and matched control subjects by using tandem mass tags (TMT) technology. More than 500 proteins were identified with quantification, and 48 of them showed significant difference expression (p < 0.05) between normal controls and gastric cancer patients, including 7 up-regulated proteins and 41 down-regulated proteins. Five proteins were selected for initial verification by ELISA and three were successfully verified, namely cystatin B (CSTB), triosephosphate isomerase (TPI1), and deleted in malignant brain tumors 1 protein (DMBT1). All three proteins could differentiate gastric cancer patients from normal control subjects, dramatically (p < 0.05). The combination of these three biomarkers could reach 85% sensitivity and 80% specificity for the detection of gastric cancer with accuracy of 0.93. This study provides the proof of concept of salivary biomarkers for the non-invasive detection of gastric cancer. It is highly encouraging to turn these biomarkers into an applicable clinical test after large scale validation.