Abstract
Exosomes are nano-sized membranous vesicles of endosomal origin that carry nucleic acids, lipids and proteins. The cargo of exosomes is cell origin specific and the release of these exosomes and uptake by an acceptor cell is seen as a vital element of cell-cell communication. Here, we sought to investigate the diagnostic and prognostic value of the expression of glypican 3 (GPC3) on primary gastro-esophageal adenocarcinoma (GEA) tissue (tGPC3) and corresponding serum exosomes (eGPC3). Circulating exosomes were extracted from serum samples of 49 patients with GEA and 56 controls. Extracted exosomes were subjected to flow cytometry for the expression of eGPC3 and GPC3 expression on primary GEA tissue samples was determined by immunohistochemistry and correlated to clinicopathological parameters. We found decreased eGPC3 levels in GEA patients compared to healthy controls (p < 0.0001) and high tGPC3 expression. This was significantly associated with poor overall survival (high vs. low eGPC3: 87.40 vs. 60.93 months, p = 0.041, high vs. low tGPC3: 58.03 vs. 84.70 months, p = 0.044). Cox regressional analysis confirmed tGPC3 as an independent prognostic biomarker for GEA (p = 0.02) and tGPC3 expression was validated in two independent cohorts. Our findings demonstrate that eGPC3 and tGPC3 can be used as potential diagnostic and prognostic biomarkers for GEA.
Highlights
Gastro-esophageal adenocarcinomas (GEA) are one of the most common causes of cancer-related mortality [1], despite an overall decline in incidence [2]
We evaluated the expression of glypican 3 (GPC3) on serum-derived exosomes and corresponding primary tumor tissue in patients with GEA
We demonstrate that increased expression of GPC3 in GEA tissue is associated with decreased overall survival in the Dresden cohort and two independent cohorts including a total of 1279 patients
Summary
Gastro-esophageal adenocarcinomas (GEA) are one of the most common causes of cancer-related mortality [1], despite an overall decline in incidence [2]. GEA is a heterogeneous disease with distinct clinical subtypes and the complex molecular mechanisms underlying the initiation and progression of these cancers is not very well understood. There is an urgent need to better characterize the molecular mechanism underlying this disease and develop effective screening systems to facilitate earlier diagnosis and treatment [3]. A large number of novel blood-based biomarkers have been reported for their potential role in clinical practice [6]. None of these have been established in the clinic for early detection or disease monitoring. The most commonly used biomarkers for GEA are serum carbohydrate antigen 19-9 (CA-19-9), carbohydrate antigen 72-4 (CA-72-4) and carcinoembryonic antigen (CEA), it has been shown that they vary in their sensitivity and specificity and strongly depend on tumor burden [7]
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