Li Lingyun, Lan Zhongyun, Qiao Huarui, Meng Xiangjing, Shi Ziyang, Zhang Wanting, Wang Yi'ang, Sun Zengchao, Cui Qianqian, Wang Lu, Zhou Siyu, Hu Fangzheng, Zhang Daizhou, Dai Yuanyuan, Chen Hao, Geng Yong
State Key Laboratory of Drug Research, The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
State Key Laboratory of Drug Research, The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Biomaterials. 2025 Sep;320:123286. doi: 10.1016/j.biomaterials.2025.123286. Epub 2025 Mar 21.
Esophageal cancer (EC) is one of the most common causes of cancer-related mortality due in part to challenges in early diagnosis. Biomarker identification is crucial for improved early screening and treatment strategies for patients. Firstly, we employed serum proteomics techniques to screen for potential biomarkers in 15 early-stage EC patients and 5 healthy individuals. Among the differentially expressed proteins, FGL1 emerged as a promising candidate (AUC = 0.974) for early detection of EC. Subsequently, we developed NanoBiT-conjugated dual nanobodies (NBNB) sensors for robust and quantitative signal detection in fetal bovine serum (FBS) in 30 min or less, with a limit of detection (LoD) of 11.38 pM. In a case-control study recruiting 96 EC patients and 99 control samples, testing serum samples with the developed NBNB sensors revealed significantly elevated serum level of FGL1 in all-stage EC patients (AUC = 0.7880) and early-stage EC patients (AUC = 0.8286). Additionally, the combined diagnostic performance of FGL1 and CEA in EC samples is notably enhanced (AUC = 0.8847). These findings propose FGL1 as a novel and promising target for the early-stage EC diagnosis and treatment selection. Furthermore, we applied the assay to patients across six types of cancer, suggesting FGL1 as a potential pan-cancer marker. This study introduces a rapid, easy-to-use, cost-effective, reliable, universal, and high-throughput alternative to meet the growing demand for cancer biomarker testing in both academic and clinical settings.
食管癌（EC）是癌症相关死亡的最常见原因之一，部分原因是早期诊断存在挑战。生物标志物的识别对于改善患者的早期筛查和治疗策略至关重要。首先，我们采用血清蛋白质组学技术在15例早期食管癌患者和5名健康个体中筛选潜在的生物标志物。在差异表达的蛋白质中，FGL1成为早期检测食管癌的一个有前景的候选物（曲线下面积[AUC]=0.974）。随后，我们开发了纳米生物发光互补（NanoBiT）偶联双纳米抗体（NBNB）传感器，可在30分钟或更短时间内对胎牛血清（FBS）进行稳健且定量的信号检测，检测限（LoD）为11.38皮摩尔。在一项纳入96例食管癌患者和99份对照样本的病例对照研究中，用开发的NBNB传感器检测血清样本发现，各阶段食管癌患者（AUC=0.7880）和早期食管癌患者（AUC=0.8286）的血清FGL1水平显著升高。此外，FGL1和癌胚抗原（CEA）在食管癌样本中的联合诊断性能显著增强（AUC=0.8847）。这些发现表明FGL1是早期食管癌诊断和治疗选择的一个新的有前景的靶点。此外，我们将该检测方法应用于六种癌症类型的患者，提示FGL1是一种潜在的泛癌标志物。本研究引入了一种快速、易用、经济高效、可靠、通用且高通量的替代方法，以满足学术和临床环境中对癌症生物标志物检测不断增长的需求。
