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外泌体在胰腺导管腺癌进展中的作用及其作为生物标志物的潜力

The Role of Exosomes in Pancreatic Ductal Adenocarcinoma Progression and Their Potential as Biomarkers.

作者信息

Hsu Sheng-Kai, Jadhao Mahendra, Liao Wei-Ting, Chang Wen-Tsan, Lin I-Ling, Chiu Chien-Chih

机构信息

Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

出版信息

Cancers (Basel). 2023 Mar 15;15(6):1776. doi: 10.3390/cancers15061776.

DOI:10.3390/cancers15061776
PMID:36980662
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10046651/
Abstract

Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic malignancy, is an aggressive and lethal cancer with a dismal five-year survival rate. Despite remarkable improvements in cancer therapeutics, the clinical outcome of PDAC patients remains poor due to late diagnosis of the disease. This highlights the importance of early detection, wherein biomarker evaluation including exosomes would be helpful. Exosomes, small extracellular vesicles (sEVs), are cell-secreted entities with diameters ranging from 50 to 150 nm that deliver cellular contents (e.g., proteins, lipids, and nucleic acids) from parent cells to regulate the cellular processes of targeted cells. Recently, an increasing number of studies have reported that exosomes serve as messengers to facilitate stromal-immune crosstalk within the PDAC tumor microenvironment (TME), and their contents are indicative of disease progression. Moreover, evidence suggests that exosomes with specific surface markers are capable of distinguishing patients with PDAC from healthy individuals. Detectable exosomes in bodily fluids (e.g., blood, urine, saliva, and pancreatic juice) are omnipresent and may serve as promising biomarkers for improving early detection and evaluating patient prognosis. In this review, we shed light on the involvement of exosomes and their cargos in processes related to disease progression, including chemoresistance, angiogenesis, invasion, metastasis, and immunomodulation, and their potential as prognostic markers. Furthermore, we highlight feasible clinical applications and the limitations of exosomes in liquid biopsies as tools for early diagnosis as well as disease monitoring. Taking advantage of exosomes to improve diagnostic capacity may provide hope for PDAC patients, although further investigation is urgently needed.

摘要

胰腺导管腺癌(PDAC)是最常见的胰腺恶性肿瘤,是一种侵袭性致死性癌症,五年生存率极低。尽管癌症治疗有了显著进展,但由于疾病诊断较晚,PDAC患者的临床结局仍然很差。这凸显了早期检测的重要性,其中包括外泌体在内的生物标志物评估会有所帮助。外泌体是一种小细胞外囊泡(sEVs),是细胞分泌的实体,直径范围为50至150纳米,可从亲代细胞传递细胞内容物(如蛋白质、脂质和核酸),以调节靶细胞的细胞过程。最近,越来越多的研究报告称,外泌体作为信使促进了PDAC肿瘤微环境(TME)内的基质-免疫串扰,其内容物指示疾病进展。此外,有证据表明,具有特定表面标志物的外泌体能够区分PDAC患者和健康个体。体液(如血液、尿液、唾液和胰液)中可检测到的外泌体无处不在,可能作为有前景的生物标志物用于改善早期检测和评估患者预后。在这篇综述中,我们阐述了外泌体及其货物在与疾病进展相关的过程中的作用,包括化疗耐药、血管生成、侵袭、转移和免疫调节,以及它们作为预后标志物的潜力。此外,我们强调了外泌体在液体活检中作为早期诊断和疾病监测工具的可行临床应用及局限性。利用外泌体提高诊断能力可能为PDAC患者带来希望,尽管迫切需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd5c/10046651/bec1c1a5ea3b/cancers-15-01776-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd5c/10046651/e0e5778439b6/cancers-15-01776-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd5c/10046651/bec1c1a5ea3b/cancers-15-01776-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd5c/10046651/e0e5778439b6/cancers-15-01776-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd5c/10046651/bec1c1a5ea3b/cancers-15-01776-g002.jpg

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本文引用的文献

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A review on exosomes application in clinical trials: perspective, questions, and challenges.外泌体在临床试验中的应用综述:观点、问题与挑战。
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CD63-positive extracellular vesicles are potential diagnostic biomarkers of pancreatic ductal adenocarcinoma.CD63阳性细胞外囊泡是胰腺导管腺癌潜在的诊断生物标志物。
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