血清外泌体和血清磷脂酰肌醇蛋白聚糖-1与胰腺导管腺癌的早期复发相关。

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

作者信息

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

机构信息

Biotherapy Center, Harbin Medical University Cancer Hospital, Harbin, China.

Department of interventional oncology, Taizhou Municipal Hospital, Taizhou, Zhejiang, China.

出版信息

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

DOI:10.3389/fonc.2022.992929

PMID:36313694

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9614098/

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.

摘要

背景

血清外泌体磷脂酰肌醇蛋白聚糖1（GPC-1）在胰腺导管腺癌（PDAC）中的诊断效能及预后价值仍存在争议。在本研究中，我们采用酶联免疫吸附测定（ELISA）检测血清外泌体GPC-1，并确定其是否可作为早期PDAC诊断及复发的预测指标。

方法

收集50例PDAC患者、6例胰腺良性肿瘤（BPT）患者、9例慢性胰腺炎（CP）患者及50例健康对照（HC）的血清样本。使用外泌体分离试剂盒分离血清外泌体。采用ELISA检测外泌体及血清GPC-1水平。进行冻融处理以分析GPC-1的稳定性。采用受试者工作特征（ROC）分析评估GPC-1的诊断价值。采用Kaplan-Meier法及多因素Cox分析评估GPC-1的预后价值。

结果

血清外泌体及血清GPC-1的平均浓度分别为1.5 ng/ml和0.8 ng/ml。在反复冻融情况下（第1 - 5次冻融循环与第0次相比，P > 0.05），GPC-1表达水平稳定。与HC相比，PDAC患者的血清外泌体及血清GPC-1显著升高（P < 0.0001），但与CP和BPT患者相比略高（P > 0.05）。PDAC、CP和BPT患者术后5天，外泌体及血清GPC-1表达水平升高（P < 0.05）。外泌体及血清GPC-1水平高的患者无复发生存期（RFS）较短（P = 0.006和P = 0.010）。多因素分析显示，血清外泌体及血清GPC-1是早期RFS的独立预后指标（P = 0.008和P = 0.041）。