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通过检测围手术期血清中 O-糖基化改变的细胞外囊泡来预测 PDAC 的预后。

Prognosis prediction of PDAC via detection of O-glycan altered extracellular vesicles in perioperative sera.

机构信息

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan.

出版信息

Cancer Sci. 2024 Nov;115(11):3718-3728. doi: 10.1111/cas.16341. Epub 2024 Sep 16.

DOI:10.1111/cas.16341
PMID:39285510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11531947/
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy due to the difficulty in diagnosis and poor prognosis because of the high recurrence rate, necessitating reliable biomarkers to improve the diagnosis and prognosis. However, the existing markers have limitations. We previously identified extracellular vesicles (EVs) recognized by O-glycan-binding lectins (Amaranthus caudatus agglutinin [ACA]) as a novel diagnostic biomarker for PDAC using an EV-counting system (ExoCounter). This retrospective study analyzed changes in ACA-positive EVs in perioperative PDAC serum and its association with prognosis using ExoCounter. Absolute EV levels in the pre- and postoperative sera of 44 patients who underwent curative pancreatectomy for PDAC were quantified using ExoCounter. The carbohydrate antigen 19-9 levels declined in most samples postoperatively, and presented no correlation with poor prognosis. In contrast, ACA-positive EVs increased in serum at 7 days postoperatively in 27 of 44 patients (61.4%). We therefore divided participants with ACA-positive EVs before and after surgery into elevation and decline groups. The overall survival (OS) and recurrence-free survival (RFS) of patients with higher ACA-positive EVs were significantly shorter than those with lower ACA-positive EVs (26.1 months vs. not reached, P = 0.018; 11.9 vs. 38.6 months, P = 0.013). Multivariable analysis revealed that ACA-positive EV elevation in postoperative serum was an independent prognostic factor for poor OS (hazard ratio [HR] = 3.891, P = 0.023) and RFS (HR = 2.650, P = 0.024). The detection of ACA-positive EVs in perioperative serum may be used to predict the prognosis of PDAC in the early postoperative period.

摘要

胰腺导管腺癌 (PDAC) 是一种致命的恶性肿瘤,由于诊断困难和预后不良,因为高复发率,需要可靠的生物标志物来改善诊断和预后。然而,现有的标志物存在局限性。我们之前使用 EV 计数系统 (ExoCounter) 发现了被 O-糖结合凝集素 (Amaranthus caudatus agglutinin [ACA]) 识别的细胞外囊泡 (EVs) 是 PDAC 的一种新型诊断生物标志物。这项回顾性研究使用 ExoCounter 分析了围手术期 PDAC 血清中 ACA 阳性 EV 的变化及其与预后的关系。使用 ExoCounter 定量分析了 44 例接受根治性胰腺切除术的 PDAC 患者术前和术后血清中 EV 的绝对水平。大多数样本在术后 CA19-9 水平下降,与预后不良无相关性。相比之下,27 例患者在术后 7 天血清中 ACA 阳性 EV 增加(44 例患者中的 61.4%)。因此,我们将术前和术后 ACA 阳性 EV 的患者分为升高和下降组。与 ACA 阳性 EV 较低的患者相比,升高组患者的总生存 (OS) 和无复发生存 (RFS) 明显缩短 (26.1 个月 vs. 未达到,P=0.018;11.9 个月 vs. 38.6 个月,P=0.013)。多变量分析显示,术后血清中 ACA 阳性 EV 的升高是 OS(风险比 [HR]=3.891,P=0.023)和 RFS(HR=2.650,P=0.024)不良的独立预后因素。围手术期血清中 ACA 阳性 EV 的检测可能用于预测 PDAC 术后早期的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4983/11531947/d2d0c2ff7406/CAS-115-3718-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4983/11531947/8943508a5bae/CAS-115-3718-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4983/11531947/d826b421b520/CAS-115-3718-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4983/11531947/3c9805e00e73/CAS-115-3718-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4983/11531947/d2d0c2ff7406/CAS-115-3718-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4983/11531947/8943508a5bae/CAS-115-3718-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4983/11531947/d826b421b520/CAS-115-3718-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4983/11531947/3c9805e00e73/CAS-115-3718-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4983/11531947/d2d0c2ff7406/CAS-115-3718-g005.jpg

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