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联合外泌体 GPC1、CD82 和血清 CA19-9 作为多重靶标:一种用于胰腺癌诊断的特异性、灵敏性和重现性检测面板。

Combined Exosomal GPC1, CD82, and Serum CA19-9 as Multiplex Targets: A Specific, Sensitive, and Reproducible Detection Panel for the Diagnosis of Pancreatic Cancer.

机构信息

Department of Oncological Surgery, Hanzhong 3201 Hospital Affiliated to Xi'an Jiaotong University, Hanzhong, China.

Department of Pharmacy, Hebei General Hospital, Shijiazhuang, China.

出版信息

Mol Cancer Res. 2020 Feb;18(2):300-310. doi: 10.1158/1541-7786.MCR-19-0588. Epub 2019 Oct 29.

Abstract

Pancreatic cancer is a highly lethal malignancy with poor prognosis due to the lack of early symptoms and resultant late diagnosis. Thus, it is extremely urgent to establish a simple and effective method for the early diagnosis of pancreatic cancer. Although some studies have provided positive evidence for the use of exosomal surface protein glypican-1 (GPC1) as a biomarker for early screening, its clinical application is still controversial. Here, we systematically verified the role of exosomal GPC1 as a potential screening biomarker. First, bottleneck problems of a stable detection method and an identification standard were systematically studied, and a Python-based standardized data processing method was established to analyze exosomal GPC1 expression. Second, a detection panel consisting of exosomal GPC1, exosomal cluster of differentiation 82 (CD82), and serum carbohydrate antigen 19-9 (CA19-9) was employed for pancreatic cancer detection. This panel exhibited excellent diagnostic results (AUC = 0.942) and could effectively distinguish healthy people from patients with pancreatic cancer ( value threshold = 0.2282) and patients with pancreatitis from patients with pancreatic cancer ( value threshold = 0.5467). IMPLICATIONS: These results indicate that the combined detection of exosomal GPC1, exosomal CD82, and serum CA19-9 shows great promise as a standard method for pancreatic cancer detection and that this panel could be further applied for screening pancreatic cancer in Chinese populations.

摘要

胰腺癌是一种高度致命的恶性肿瘤,由于缺乏早期症状,导致诊断较晚,预后较差。因此,建立一种简单有效的胰腺癌早期诊断方法迫在眉睫。虽然一些研究为外泌体表面蛋白磷脂酰基醇蛋白聚糖-1(GPC1)作为早期筛查的生物标志物提供了积极的证据,但它的临床应用仍存在争议。在这里,我们系统地验证了外泌体 GPC1 作为一种潜在的筛查生物标志物的作用。首先,我们系统地研究了稳定检测方法和鉴定标准的瓶颈问题,并建立了一个基于 Python 的标准化数据处理方法来分析外泌体 GPC1 的表达。其次,我们采用了由外泌体 GPC1、外泌体 CD82 和血清碳水化合物抗原 19-9(CA19-9)组成的检测面板来检测胰腺癌。该面板表现出优异的诊断结果(AUC=0.942),能够有效地区分健康人群与胰腺癌患者(值阈值=0.2282)以及胰腺炎患者与胰腺癌患者(值阈值=0.5467)。意义:这些结果表明,外泌体 GPC1、外泌体 CD82 和血清 CA19-9 的联合检测有望成为胰腺癌检测的标准方法,该检测面板可进一步应用于中国人群的胰腺癌筛查。

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