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胰腺导管腺癌及对照患者的无细胞血浆 microRNA。

Cell-free plasma microRNA in pancreatic ductal adenocarcinoma and disease controls.

机构信息

From the *Department of Clinical Biochemistry, Immunology & Genetics, Statens Serum Institut, Copenhagen; †Department of Medical Gastroenterology, Odense University Hospital, Odense; and ‡Medical Prognosis Institute, Hørsholm, Denmark.

出版信息

Pancreas. 2013 Oct;42(7):1107-13. doi: 10.1097/MPA.0b013e318296bb34.

Abstract

OBJECTIVES

There are no tumor-specific biochemical markers for pancreatic ductal adenocarcinoma (PDAC). Tissue-specific gene expression including microRNA (miRNA) profiling, however, identifies specific PDAC signatures. This study evaluates associations between circulating, cell-free plasma-miRNA profiles and PDAC in a disease and disease-control cohort.

METHODS

We performed a microarray profiling of 847 different mature miRNAs from plasma in an exploratory cohort of 20 patients with PDAC or other pancreatic diseases, profiling of 45 miRNAs in plasma samples from PDAC (n = 48) and disease controls (n = 47), and evaluation of associations of data with diagnosis, survival, and CA-19-9.

RESULTS

We find 7 significantly deregulated miRNAs in PDAC using univariate statistics. At a false-discovery rate of 5%, miRNA-375 remained significantly elevated in PDAC. MicroRNA-375 did not improve diagnosis of PDAC in this cohort (70% accuracy) and did not correlate with survival. However, 3 controls (other gastrointestinal cancers) with increased CA-19-9 did not show increased miRNA-375.

CONCLUSIONS

In the plasma-miRNA population, we find miRNA-375, which is selectively expressed in the endocrine pancreas under normal conditions, increased in PDAC cases compared with patients with other pancreatic or gastrointestinal diseases. The miRNA-375 does not outperform CA-19-9 diagnostically in the present cohort. However, it shows promising specificity and should be examined in larger prospective studies.

摘要

目的

目前尚无针对胰腺导管腺癌 (PDAC) 的肿瘤特异性生化标志物。然而,组织特异性基因表达,包括 microRNA (miRNA) 谱分析,可确定特定的 PDAC 特征。本研究评估了循环无细胞血浆 miRNA 谱与疾病和疾病对照组中 PDAC 之间的关联。

方法

我们对 20 例 PDAC 或其他胰腺疾病患者的血浆中 847 种不同成熟 miRNA 进行了微阵列分析,对 45 种 miRNA 进行了 PDAC (n=48)和疾病对照 (n=47)血浆样本的分析,并评估了数据与诊断、生存和 CA-19-9 的相关性。

结果

我们使用单变量统计发现了 7 种在 PDAC 中明显失调的 miRNA。在假发现率为 5%的情况下,miRNA-375 在 PDAC 中仍显著升高。在该队列中,miRNA-375 并未改善 PDAC 的诊断(准确率为 70%),也与生存无关。然而,3 例(其他胃肠道癌)CA-19-9 升高的对照组并未显示 miRNA-375 升高。

结论

在血浆 miRNA 群体中,我们发现 miRNA-375 在正常情况下在胰岛中选择性表达,与其他胰腺或胃肠道疾病患者相比,PDAC 病例中增加。在本队列中,miRNA-375 在诊断上并不优于 CA-19-9。然而,它显示出有希望的特异性,应在更大的前瞻性研究中进行检查。

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