A microRNA signature in circulating exosomes is superior to exosomal glypican-1 levels for diagnosing pancreatic cancer.

A microRNA signature in circulating exosomes is superior to exosomal glypican-1 levels for diagnosing pancreatic cancer.
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DOI:
10.1016/j.canlet.2017.02.019
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发表时间:
2017-05-01
期刊:
影响因子:
9.7
通讯作者:
Korc M
Korc M
中科院分区:
医学1区
文献类型:
--
作者:
Lai X;Wang M;McElyea SD;Sherman S;House M;Korc M

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胰腺导管腺癌(PDAC)是一种临床上常表现为晚期的致命恶性肿瘤,可能与慢性胰腺炎(CP)相混淆。相反,CP可能被误诊为PDAC,导致不必要的胰腺切除术。因此,PDAC的早期诊断和PDAC与CP的明确区分对于改善护理至关重要。外泌体是一种循环的微囊泡,其成分可以作为癌症生物标志物。我们比较了正常对照组和PDAC和CP患者的外泌体glypican-1 (GPC1)和microRNA水平。我们报道外泌体GPC1不能诊断PDAC,而高水平的外泌体microRNA-10b, (miR-10b), miR-21, miR-30c和miR-181a和低水平的miR-let7a很容易将PDAC与正常对照和CP样本区分。与GPC1相比,PDAC切除后24小时内升高的外泌体miR水平降至正常值。所有29例PDAC患者的外泌体miR-10b和miR-30c水平均显著升高,而8例患者的CA 19-9水平正常或略有升高。因此,我们的外泌体miR信号在诊断PDAC和区分PDAC和CP方面优于外泌体GPC1或血浆CA 19-9水平。
Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that often presents clinically at an advanced stage and that may be confused with chronic pancreatitis (CP). Conversely, CP may be misdiagnosed as PDAC leading to unwarranted pancreas resection. Therefore, early PDAC diagnosis and clear differentiation between PDAC and CP are crucial for improved care. Exosomes are circulating micro-vesicles whose components can serve as cancer biomarkers. We compared exosomal glypican-1 (GPC1) and microRNA levels in normal control subjects and in patients with PDAC and CP. We report that exosomal GPC1 is not diagnostic for PDAC, whereas high exosomal levels of microRNA-10b, (miR-10b), miR-21, miR-30c, and miR-181a and low miR-let7a readily differentiate PDAC from normal control and CP samples. By contrast with GPC1, elevated exosomal miR levels decreased to normal values within 24 h following PDAC resection. All 29 PDAC cases exhibited significantly elevated exosomal miR-10b and miR-30c levels, whereas 8 cases had normal or slightly increased CA 19-9 levels. Thus, our exosomal miR signature is superior to exosomal GPC1 or plasma CA 19-9 levels in establishing a diagnosis of PDAC and differentiating between PDAC and CP.