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用于诊断结直肠癌的血清肽组分析:在两个独立队列中的发现与验证

Serum peptidome profiling for the diagnosis of colorectal cancer: discovery and validation in two independent cohorts.

作者信息

Wang Hao, Luo Chenghua, Zhu Shengtao, Fang Honghong, Gao Qing, Ge Siqi, Qu Haixia, Ma Qingwei, Ren Hongwei, Wang Youxin, Wang Wei

机构信息

Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China.

Department of Retroperitoneal Tumors Surgery, Peking University International Hospital, Beijing 102206, China.

出版信息

Oncotarget. 2017 Jul 26;8(35):59376-59386. doi: 10.18632/oncotarget.19587. eCollection 2017 Aug 29.

DOI:10.18632/oncotarget.19587
PMID:28938643
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5601739/
Abstract

Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Except for the existing fecal occult blood test, colonoscopy and sigmoidoscopy, no widely accepted diagnostic methods have been available. To identify potential peptide biomarkers for CRC, serum samples from a discovery cohort (100 CRC patients and 100 healthy controls) and an independent validation cohort (91 CRC patients and 91 healthy controls) were collected. Peptides were fractionated by weak cation exchange magnetic beads (MB-WCX) and analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Five peptides (peaks at 1895.3, 2020.9, 2080.7, 2656.8 and 3238.5) were identified as candidate biomarkers for CRC. A diagnostic panel based on the five peptides can discriminate CRC patients from healthy controls, with an accuracy of 91.8%, sensitivity of 95.6%, and specificity of 87.9% in the validation cohort. Peptide peaks at 1895.3, 2020.9 and 3238.5 were identified as the partial sequences of complement component 4 (C4), complement component 3 (C3) and fibrinogen α chain (FGA), respectively. This study potentiated peptidomic analysis as a promising diagnostic tool for diagnosis of CRC. The identified peptides suggest the involvement of the C3, C4 and FGA in CRC pathogenesis.

摘要

结直肠癌(CRC)是全球最常见的恶性肿瘤之一。除了现有的粪便潜血试验、结肠镜检查和乙状结肠镜检查外,尚无广泛接受的诊断方法。为了鉴定CRC潜在的肽生物标志物,收集了来自发现队列(100例CRC患者和100例健康对照)和独立验证队列(91例CRC患者和91例健康对照)的血清样本。肽通过弱阳离子交换磁珠(MB-WCX)进行分离,并通过基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF MS)进行分析。五种肽(峰分别位于1895.3、2020.9、2080.7、2656.8和3238.5)被鉴定为CRC的候选生物标志物。基于这五种肽的诊断面板可以区分CRC患者和健康对照,在验证队列中的准确率为91.8%,灵敏度为95.6%,特异性为87.9%。峰位于1895.3、2020.9和3238.5的肽分别被鉴定为补体成分4(C4)、补体成分3(C3)和纤维蛋白原α链(FGA)的部分序列。本研究增强了肽组学分析作为一种有前景的CRC诊断工具的作用。所鉴定的肽提示C3、C4和FGA参与了CRC的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/5601739/fb9ab0101cc3/oncotarget-08-59376-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/5601739/643e6867973c/oncotarget-08-59376-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/5601739/2d62c238f050/oncotarget-08-59376-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/5601739/fb9ab0101cc3/oncotarget-08-59376-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/5601739/643e6867973c/oncotarget-08-59376-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/5601739/2d62c238f050/oncotarget-08-59376-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/129e/5601739/fb9ab0101cc3/oncotarget-08-59376-g003.jpg

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