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Circulating microRNAs in Pancreatic Juice as Candidate Biomarkers of Pancreatic Cancer

机译:胰腺汁中的循环微RNA作为胰腺癌的候选生物标志物

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摘要

Development of sensitive and specific biomarkers, preferably those circulating in body fluids is critical for early diagnosis of cancer. This study performed profiling of microRNAs (miRNAs) in exocrine pancreatic secretions (pancreatic juice) by microarray analysis utilizing pancreatic juice from 6 pancreatic ductal adenocarcinoma (PDAC) patients and two pooled samples from 6 non-pancreatic, non-healthy (NPNH) as controls. Differentially circulating miRNAs were subsequently validated in 88 pancreatic juice samples from 50 PDAC, 19 chronic pancreatitis (CP) patients and 19 NPNH controls. A marked difference in the profiles of four circulating miRNAs (miR-205, miR-210, miR-492, and miR-1427) was observed in pancreatic juice collected from patients with PDAC and those without pancreatic disease. Elevated levels of the four miRNAs together predicted PDAC with a specificity of 88% and sensitivity of 87%. Inclusion of serum CA19-9 level increased the sensitivity to 91% and the specificity to 100%. Enrichment of the four miRNAs in pancreatic juice was associated with decreased OS, as was the combination of miR-205 and miR-210. Higher contents of miR-205 and miR-210 were also associated with lymph node metastasis. Elevated levels of circulating miR-205, miR-210, miR-492, and miR-1247 in pancreatic juice are, therefore, promising candidate biomarkers of disease and poor prognosis in patients with PDAC.
机译:敏感和特异性生物标志物的开发,最好是在体液中循环的那些生物标志物,对于癌症的早期诊断至关重要。这项研究利用6例胰腺导管腺癌(PDAC)患者的胰液和6例非胰腺,非健康(NPNH)的2个合并样品,通过微阵列分析对外分泌胰腺分泌物(胰液)中的microRNA(miRNA)进行了分析。随后在来自50个PDAC,19个慢性胰腺炎(CP)患者和19个NPNH对照的88个胰液样品中验证了差异循环的miRNA。在从患有PDAC的患者和没有胰腺疾病的患者那里收集的胰腺汁液中,观察到四种循环miRNA(miR-205,miR-210,miR-492和miR-1427)的轮廓存在显着差异。四个miRNA的水平升高共同预测PDAC的特异性为88%,敏感性为87%。包含血清CA19-9水平可将敏感性提高到91%,将特异性提高到100%。胰腺汁中四种miRNA的富集与OS降低有关,miR-205和miR-210的组合也与OS降低有关。 miR-205和miR-210的含量较高也与淋巴结转移有关。因此,胰腺汁中循环miR-​​205,miR-210,miR-492和miR-1247的水平升高,是PDAC患者疾病和预后不良的有希望的生物标志物。

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