探讨胰腺癌中上皮-间质转化相关的外泌体 microRNA 标志物。

Exploration of Exosomal Micro RNA Biomarkers Related to Epithelial-to-Mesenchymal Transition in Pancreatic Cancer.

机构信息

Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.

Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan

出版信息

Anticancer Res. 2020 Apr;40(4):1843-1853. doi: 10.21873/anticanres.14138.

DOI:10.21873/anticanres.14138

PMID:32234872

Abstract

BACKGROUND/AIM: Epithelial-to-mesenchymal transition (EMT) plays important roles in cancer progression. This study aimed to identify the exosomal miRNA (exo-miRNA) profiles related to the EMT status in pancreatic cancer (PC).

MATERIALS AND METHODS

Comprehensive exo-miRNA-expression profiles in the culture media of PC cell lines were analyzed through microarray technology. The identified miRNAs were analyzed to investigate their clinical implication using The Cancer Genome Atlas (TCGA) dataset and clinical samples.

RESULTS

We prioritized 291 exo-miRNAs differentially expressed between epithelial and mesenchymal cell types. Among them, survival analysis based on the TCGA dataset revealed that mir-196b and mir-204 significantly stratify the prognosis of PC cases. In addition, analysis of cell lines indicated miR-196b-3p as a mesenchymal marker and miR-204-3p as an epithelial marker. Finally, we demonstrated that miR-196b-3p and miR-204-3p in serum exosomes were differentially expressed among intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, and PC.

CONCLUSION

Serum exo-miRNA biomarkers potentially identify the pancreatic tumor status through less-invasive methods.

摘要

背景/目的：上皮-间充质转化（EMT）在癌症进展中发挥重要作用。本研究旨在鉴定与胰腺癌（PC）中 EMT 状态相关的外泌体 miRNA（exo-miRNA）谱。

材料和方法

通过微阵列技术分析 PC 细胞系培养物中的综合 exo-miRNA 表达谱。使用癌症基因组图谱（TCGA）数据集和临床样本分析鉴定的 miRNA，以研究其临床意义。

结果

我们在上皮和间充质细胞类型之间优先确定了 291 个差异表达的外泌体 miRNA。其中，基于 TCGA 数据集的生存分析显示，mir-196b 和 mir-204 显著分层 PC 病例的预后。此外，细胞系分析表明 miR-196b-3p 作为间充质标志物，miR-204-3p 作为上皮标志物。最后，我们证明血清外泌体中的 miR-196b-3p 和 miR-204-3p 在导管内乳头状黏液性肿瘤、黏液性囊腺瘤和 PC 之间存在差异表达。