DOI: 10.1097/mpa.0000000000002315 ISSN: 1536-4828

Liquid Biopsy for Pancreatic Cancer by Serum Extracellular Vesicle–Encapsulated Long Noncoding RNA HEVEPA

Kenji Takahashi, Tatsutoshi Inuzuka, Yuta Shimizu, Kazuki Sawamoto, Kenzui Taniue, Yusuke Ono, Fumi Asai, Kazuya Koyama, Hiroki Sato, Hidemasa Kawabata, Hidetaka Iwamoto, Keisuke Yamakita, Yohei Kitano, Takashi Teramoto, Mikihiro Fujiya, Satoshi Fujii, Yusuke Mizukami, Toshikatsu Okumura
  • Endocrinology
  • Hepatology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine
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Objectives

The role of long noncoding RNAs (lncRNAs) in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Extracellular vesicle (EV)–encapsulated RNAs could be effective targets for liquid biopsy. We aimed to identify previously unknown EV-encapsulated lncRNAs in PDAC and establish highly accurate methods for isolating EVs.

Materials and Methods

Extracellular vesicles were isolated using existing and newly developed methods, namely, PEViA-UC and PEViA-IP, from serum samples of 20 patients with PDAC, 22 patients with intraductal papillary mucinous neoplasms, and 21 healthy individuals. Extracellular vesicle lncRNA expression was analyzed using digital PCR.

Results

Gene expression analysis using cDNA microarray revealed a highly expressed lncRNA, HEVEPA, in serum EVs from patients with PDAC. We established PEViA-UC and PEViA-IP using PEViA reagent, ultracentrifugation, and immunoprecipitation. Although detection of EV-encapsulated HEVEPA using existing methods is challenging, PEViA-UC and PEViA-IP detected EV HEVEPA, which was highly expressed in patients with PDAC compared with non-PDAC patients. The detection sensitivity for discriminating PDAC from non-PDAC using the combination of HEVEPA and HULC, which are highly expressed lncRNAs in PDAC, and carbohydrate antigen 19-9 (CA19-9), was higher than that of HEVEPA, HULC, or CA19-9 alone.

Conclusions

Extracellular vesicle lncRNAs isolated using PEViA-IP and CA19-9 together could be effective targets in liquid biopsy for PDAC diagnosis.

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