Serum exosomal and serum glypican-1 are associated with early recurrence of pancreatic ductal adenocarcinoma

Juan Zhao; Madi Guo; Yushuai Song; Shan Liu; Ran Liao; Yu Zhang; Yumin Zhang; Qi Yang; Yuanlong Gu; Xiaoyi Huang

doi:10.3389/fonc.2022.992929

Serum exosomal and serum glypican-1 are associated with early recurrence of pancreatic ductal adenocarcinoma

Front Oncol. 2022 Oct 14:12:992929. doi: 10.3389/fonc.2022.992929. eCollection 2022.

Authors

Juan Zhao¹, Madi Guo¹, Yushuai Song¹, Shan Liu¹, Ran Liao¹, Yu Zhang¹, Yumin Zhang¹, Qi Yang¹, Yuanlong Gu², Xiaoyi Huang^{1

3}

Affiliations

¹ Biotherapy Center, Harbin Medical University Cancer Hospital, Harbin, China.
² Department of interventional oncology, Taizhou Municipal Hospital, Taizhou, Zhejiang, China.
³ NHC Key Laboratory of Cell Transplantation, Harbin Medical University, Harbin, Heilongjiang, China.

Abstract

Background: The diagnostic performance and prognostic value of serum exosomal glypican 1 (GPC-1) in pancreatic ductal adenocarcinoma (PDAC) remain controversial. In this study, we detected serum exosomal GPC-1 using enzyme-linked immunosorbent assay (ELISA) and determined whether it serves as a predictor of diagnosis and recurrence for early-stage PDAC.

Methods: Serum samples were obtained from patients with 50 PDAC, 6 benign pancreatic tumor (BPT), or 9 chronic pancreatitis (CP) and 50 healthy controls (HCs). Serum exosomes were isolated using an exosome isolation kit. Exosomal and serum GPC-1 levels were measured using ELISA. The freeze-thaw process was carried out to analyze the stability of GPC-1. Receiver operating characteristic (ROC) analysis was employed to assess the diagnostic value of GPC-1. Kaplan-Meier and multivariate Cox analyses were used to evaluate the prognostic value of GPC-1.

Results: The average concentrations of serum exosomal and serum GPC-1 were 1.5 and 0.8 ng/ml, respectively. GPC-1 expression levels were stable under repeated freezing and thawing (d1-5 freeze-thaw cycles vs. d0 P > 0.05). Serum exosomal and serum GPC-1 were significantly elevated in patients with PDAC compared with HCs (P < 0.0001) but were slightly higher compared with that in patients with CP and BPT (P > 0.05). The expression levels of exosomal and serum GPC-1 were elevated 5 days after surgery in patients with PDAC, CP, and BPT (P < 0.05). Patients with high levels of exosomal and serum GPC-1 had a shorter relapse-free survival (RFS) (P = 0.006, and P = 0.010). Multivariate analyses showed that serum exosomal and serum GPC-1 were independent prognostic indicators for early RFS (P = 0.008, and P = 0.041).

Conclusion: ELISA is an effective and sensitive method to detect exosomal and serum GPC-1. The detection of GPC-1 was stable under repeated freezing and thawing cycles and could distinguish early-stage PDAC from HCs but not CP and BPT. Exosomal and serum GPC-1 may be good independent predictors of early recurrence in early-stage PDAC.

Keywords: diagnosis; early recurrence; exosome; glypican 1; pancreatic ductal adenocarcinoma.