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

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 differen-tiation 82 (CD82), and serum carbohydrate antigen 19-9 (CA19-9) was employed for pancreatic cancer detection. This panel exhibited excellent diagnostic results (AUC ¼ 0.942) and could effectively distinguish healthy people from patients with pancreatic cancer (P value threshold ¼ 0.2282) and patients with pancreatitis from patients with pancreatic cancer (P value threshold ¼ 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.

Identification of Five Glycolysis-Related Gene Signature and Risk Score Model for Colorectal Cancer

“…GPC1+ circulating exosomes were regarded as a therapeutic target (34) and could facilitate the early detection of cancer (33). Another study demonstrated that combined detection of exosomal GPC1, exosomal CD82, and serum CA19-9 shows excellent promise as a standard method for pancreatic cancer detection (35). Likewise, P4HA1 is the active catalytic component of prolyl 4-hydroxylase and has been reported to promote tumor progression and metastasis in several cancers (36)(37)(38).…”

The function and clinical application of extracellular vesicles in innate immune regulation

“…Furthermore, the combined detection of exosomal GPC1, exosomal CD82, and serum CA19-9 shows great promise as a standard method for PC detection. 183 Another study has shown that the determination of S100B and MIA in exosomes may be an alternative to their analysis in serum for the diagnosis and prognosis of melanoma patients. 184 In addition, exosomal cytoskeleton-associated protein 4 (CKAP4), a novel DKK1 receptor, may represent a biomarker for pancreatic cancer.…”

A Prognostic Prediction Model Developed Based on Four CpG Sites and Weighted Correlation Network Analysis Identified DNAJB1 as a Novel Biomarker for Pancreatic Cancer

“…Therefore, the development of a risk stratification model may help clinicians to design personalized treatment programs for different patients. Previous studies have proposed various risk stratification models for the diagnosis, prognosis, and recurrence of pancreatic cancer, which exhibited better efficiency than the classical TNM stage (43)(44)(45). The rapid development of sequencing techniques has enabled the access to multi-omics data and high-quality clinical information through different databases, such as TCGA, ICGC, and Gene Expression Omnibus (17,46,47).…”