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Single-Molecule Liquid Biopsy Detects Low- and High-Abundance Protein Markers Simultaneously for Pancreatic Cancer Diagnosis

化学 丰度(生态学) 液体活检 胰腺癌 分子 癌症 内科学 有机化学 医学 渔业 生物
作者
Xinjian Wang,Yongsheng Che,Songlin Liu,Bochen Ma,Yijun Liu,Jiao Lei,Yuan Liang,Yuxun Zhou,Jieer Ying,Yimin Zhang,Tian Chen,Tao Zhu,Lubin Qi,Yifei Jiang,Xiaohong Fang
出处
期刊:Analytical Chemistry [American Chemical Society]
标识
DOI:10.1021/acs.analchem.4c07031
摘要

Simultaneous analysis of multiple biomarkers can typically improve the sensitivity and specificity of a disease diagnosis. Low-abundance serum proteins have recently emerged as a novel class of biomarkers for diseases. Due to the low concentration, the low-abundance protein analysis relies on single-molecule immunoassay, which has a very limited dynamic range. As a result, simultaneous analysis of low- and high-abundance protein markers requires multiple instruments, which demands larger sample volumes and is cost-/labor-consuming. To overcome these limitations, we developed a single-molecule imaging technique that can detect low- and high-abundance protein markers simultaneously in one chip. By employing a hybrid biomarker capture strategy that involves both glass surface and bead immobilization, our method greatly extended the detection range of the single-molecule assay. We used the method for pancreatic cancer diagnosis and analyzed three serum biomarkers of different abundances, including LIF, CA19-9, and CA125. Combined analysis of the three biomarkers yielded exceptional sensitivity and specificity (AUC = 0.996), which is better than using any of the markers alone, including CA19-9 that is used in clinical practice (AUC = 0.804). Overall, we demonstrated a simple and cost-effective method that greatly extended the dynamic range of single-molecule imaging while maintaining the sensitivity, which has great potential in various clinical applications.
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