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对来自囊液和血清的CA19-9进行MUC1和聚糖探测所捕获的生物标志物,可增强对卵巢癌的识别。

MUC1 and glycan probing of CA19-9 captured biomarkers from cyst fluids and serum provides enhanced recognition of ovarian cancer.

作者信息

Ruma Shamima Afrin, Vinod Rufus, Jain Shruti, Huhtinen Kaisa, Hynninen Johanna, Leivo Janne, Pettersson Kim, Sundfeldt Karin, Gidwani Kamlesh

机构信息

Department of Life Technologies, Division of Biotechnology, University of Turku, Medisiina D, 5th floor, Kiinamyllynkatu 10, 20520, Turku, Finland.

Institute of Biomedicine and FICAN West Cancer Centre, University of Turku and Turku University Hospital, Turku, Finland.

出版信息

Sci Rep. 2025 Jan 25;15(1):3171. doi: 10.1038/s41598-025-86735-z.

Abstract

Glycosylation changes of circulating proteins carrying the CA19-9 antigen may offer new targets for detection methods to be explored for the diagnosis of epithelial ovarian cancer (EOC). Search for assay designs for targets initially captured by a CA19-9 antigen reactive antibody from human body fluids by probing with fluorescent nanoparticles coated with lectins or antibodies to known EOC associated proteins. CA19-9 antigens were immobilized from ascites fluids, ovarian cyst fluids or serum samples using monoclonal antibody C192 followed by probing of carrier proteins using anti-MUC16, anti-MUC1 and, anti STn antibodies and seven lectins, all separately coated on nanoparticles. Compared to reference CA19-9 and CA125 immunoassays, nanoparticle aided detection using MUC16, Ma695 and STn antibodies and lectin WGA provided, both separately and combined, improved discrimination of EOC and borderline cancers from benign samples when applied to 60 cyst fluid specimens. When applied to a panel of 44 serum samples (EOC N = 24, healthy and benign samples N = 20) two assays, CA19-9 and CA19-9, stood out with equally superior separations (p-values < 10) of the two groups compared to conventional CA19-9 immunoassay (p-value 0.03).Eu -NP based CA19-9, CA19-9, CA19-9 and CA19-9 show promise for improved EOC detection when applied to ascites & cyst fluids. When applied to circulation-derived samples, the two MUC1 based assays, CA19-9 and CA19-9 outperformed other assay constructs. Our results call for further validation in larger EOC cohorts preferentially with early stage ovarian cancers and all major histotypes against commonly occurring benign conditions.

摘要

携带CA19-9抗原的循环蛋白糖基化变化可能为上皮性卵巢癌(EOC)诊断中有待探索的检测方法提供新靶点。通过用包被有凝集素或已知EOC相关蛋白抗体的荧光纳米颗粒进行探测,寻找针对最初由CA19-9抗原反应性抗体从人体体液中捕获的靶点的检测方法设计。使用单克隆抗体C192从腹水、卵巢囊肿液或血清样本中固定CA19-9抗原,然后分别用抗MUC16、抗MUC1和抗STn抗体以及七种凝集素探测载体蛋白,所有这些都分别包被在纳米颗粒上。与参考CA19-9和CA125免疫测定相比,当应用于60个囊肿液标本时,使用MUC16、Ma695和STn抗体以及凝集素WGA的纳米颗粒辅助检测单独或联合使用时,能更好地区分EOC和交界性癌与良性样本。当应用于一组44个血清样本(EOC n = 24,健康和良性样本n = 20)时,两种检测方法CA19-9和CA19-9表现突出,与传统CA19-9免疫测定相比,两组的分离效果同样优异(p值< 10)(p值0.03)。基于铕纳米颗粒的CA19-9、CA19-9、CA19-9和CA19-9在应用于腹水和囊肿液时显示出改善EOC检测的前景。当应用于循环来源的样本时,两种基于MUC1的检测方法CA19-9和CA19-9优于其他检测构建体。我们的结果要求在更大的EOC队列中进行进一步验证,优先针对早期卵巢癌和所有主要组织学类型,与常见的良性疾病进行对比。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2704/11762729/891b235a0e30/41598_2025_86735_Fig1_HTML.jpg

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