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通过蛋白质组学方法鉴定 MST1 作为结直肠癌早期检测的潜在生物标志物。

Identification of MST1 as a potential early detection biomarker for colorectal cancer through a proteomic approach.

机构信息

Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.

Department of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, 510655, China.

出版信息

Sci Rep. 2017 Oct 27;7(1):14265. doi: 10.1038/s41598-017-14539-x.

DOI:10.1038/s41598-017-14539-x
PMID:29079854
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5660227/
Abstract

Colorectal cancer (CRC) is a common malignant neoplasm worldwide. It is important to identify new biomarkers for the early detection of CRC. In this study, magnetic beads and the Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) platform were used to analyse CRC and healthy control (HC) serum samples. The CRC diagnosis pattern was established to have a specificity of 94.7% and sensitivity of 92.3% in a blind test. The candidate biomarker serine/threonine kinase 4 (STK4, also known as MST1) was identified by Tandem mass spectrometry (MS/MS) and verified with western blotting and enzyme-linked immunosorbent assay (ELISA). The results indicated that there was a higher concentration of MST1 in HC subjects than stage I CRC patients for the early detection of CRC and a lower concentration in stage IV patients than in other CRC patients. The sensitivity and specificity of MST1 combined with carcinoembryonic antigen (CEA) and faecal occult blood test (FOBT) in diagnosis of colorectal cancer were 92.3% and 100%, respectively. Additionally, low MST1 expression was associated with the poor prognosis. These results illustrate that MST1 is a potential biomarker for early detection, prognosis and prediction of distant metastasis of CRC.

摘要

结直肠癌(CRC)是一种常见的恶性肿瘤,在全球范围内。重要的是要确定新的生物标志物,用于 CRC 的早期检测。在这项研究中,使用磁珠和基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF-MS)平台来分析 CRC 和健康对照(HC)血清样本。在盲测中,CRC 诊断模式的特异性为 94.7%,敏感性为 92.3%。通过串联质谱(MS/MS)鉴定候选生物标志物丝氨酸/苏氨酸激酶 4(STK4,也称为 MST1),并用 Western blot 和酶联免疫吸附试验(ELISA)进行验证。结果表明,在早期检测 CRC 时,HC 受试者中 MST1 的浓度高于 I 期 CRC 患者,而在 IV 期患者中低于其他 CRC 患者。MST1 联合癌胚抗原(CEA)和粪便潜血试验(FOBT)诊断结直肠癌的敏感性和特异性分别为 92.3%和 100%。此外,MST1 低表达与预后不良相关。这些结果表明,MST1 是 CRC 早期检测、预后和远处转移预测的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1123/5660227/1db95a2c6490/41598_2017_14539_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1123/5660227/c222cd4842ea/41598_2017_14539_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1123/5660227/fbd0b6aa5092/41598_2017_14539_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1123/5660227/dfb43160e379/41598_2017_14539_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1123/5660227/1db95a2c6490/41598_2017_14539_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1123/5660227/c222cd4842ea/41598_2017_14539_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1123/5660227/fbd0b6aa5092/41598_2017_14539_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1123/5660227/dfb43160e379/41598_2017_14539_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1123/5660227/1db95a2c6490/41598_2017_14539_Fig4_HTML.jpg

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