Early Detection of Pancreatic Cancer: Role of Biomarkers in Pancreatic Fluid Samples.
Early Detection of Pancreatic Cancer: Role of Biomarkers in Pancreatic Fluid Samples.
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DOI：
10.3390/diagnostics10121056
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发表时间：
2020-12-06
期刊：
影响因子：
--
通讯作者：
Ohtsuka T
中科院分区：
文献类型：
--
作者：
Ideno N;Mori Y;Nakamura M;Ohtsuka T
胰腺导管腺癌（PDAC）是全球癌症相关死亡的第四大原因。大多数PDAC患者都有症状，手术无法切除的疾病。因此，迫切需要制定早期发现策略。分子生物标志物可能在策略的各个阶段有用，以识别一般人群中的高危个体，并在高强度监测计划中检测高危病变，并结合成像方式。然而，目前可用于PDAC的生物标志物（如碳水化合物19-9 (CA19-9)）的敏感性和特异性较低，导致这种致命疾病的诊断较晚。尽管几乎所有种类的生物标志物检测都被研究过，但它们中的大多数都是在症状性疾病的背景下使用的。与其他体液相比，胰液和十二指肠液是肿瘤细胞DNA、RNA、蛋白质和外泌体的更好来源，并有可能增加这些生物标志物的敏感性/特异性。与内窥镜逆行胰胆管造影（ERCP）和内窥镜超声引导细针穿刺（EUS-FNA）收集胰腺液相比，使用十二指肠液刺激或不刺激分泌素进行DNA/蛋白质标记物试验的研究数量正在增加。基因组分析已经得到了很好的研究，基于PDAC进展模型，在胰腺液/十二指肠液中检测到的突变似乎表明存在微观前体和高度不典型增生/浸润性癌症。除了已知的在前体和PDAC中过表达的蛋白质，如CEA和S100P， PDAC患者胰液的综合蛋白质组学分析发现了许多以前未描述的蛋白质。最近发明了一种从胰液中分离外泌体的新技术，外泌体microRNA的21和155的鉴定可以作为诊断PDAC的生物标志物。由于许多研究已经探索了含有胰腺液的液体样本中的生物标志物，并报道了出色的诊断准确性，我们需要讨论如何验证这些生物标志物分析并将其用于PDAC的早期检测策略。
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths worldwide. Most patients with PDAC present with symptomatic, surgically unresectable disease. Therefore, the establishment of strategies for the early detection is urgently needed. Molecular biomarkers might be useful in various phases of a strategy to identify high-risk individuals in the general population and to detect high-risk lesions during intense surveillance programs combined with imaging modalities. However, the low sensitivity and specificity of biomarkers currently available for PDAC, such as carbohydrate 19-9 (CA19-9), contribute to the late diagnosis of this deadly disease. Although almost all classes of biomarker assays have been studied, most of them are used in the context of symptomatic diseases. Compared to other body fluids, pancreatic juice and duodenal fluid are better sources of DNA, RNA, proteins, and exosomes derived from neoplastic cells and have the potential to increase the sensitivity/specificity of these biomarkers. The number of studies using duodenal fluid with or without secretin stimulation for DNA/protein marker tests have been increasing because of the less-invasiveness in comparison to pancreatic juice collection by endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Genomic analyses have been very well-studied, and based on PDAC progression model, mutations detected in pancreatic juice/duodenal fluid seem to indicate the presence of microscopic precursors and high-grade dysplasia/invasive cancer. In addition to known proteins overexpressed both in precursors and PDACs, such as CEA and S100P, comprehensive proteomic analysis of pancreatic juice from patients with PDAC identified many proteins which were not previously described. A novel technique to isolate exosomes from pancreatic juice was recently invented and identification of exosomal microRNA’s 21 and 155 could be biomarkers for diagnosis of PDAC. Since many studies have explored biomarkers in fluid samples containing pancreatic juice and reported excellent diagnostic accuracy, we need to discuss how these biomarker assays can be validated and utilized in the strategy of early detection of PDAC.
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