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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2015; 21(28): 8527-8540
Published online Jul 28, 2015. doi: 10.3748/wjg.v21.i28.8527
Circulating RNAs as new biomarkers for detecting pancreatic cancer
Takahiro Kishikawa, Motoyuki Otsuka, Motoko Ohno, Takeshi Yoshikawa, Akemi Takata, Kazuhiko Koike
Takahiro Kishikawa, Motoyuki Otsuka, Motoko Ohno, Takeshi Yoshikawa, Akemi Takata, Kazuhiko Koike, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
Motoyuki Otsuka, Japan Science and Technology Agency, PRESTO, Kawaguchi, Saitama 332-0012, Japan
Author contributions: Kishikawa T, Otsuka M and Koike K wrote the paper; Ohno M, Yoshikawa T and Takata A prepared the Tables.
Supported by (in part) Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan, No. 25293076, No. 26860492, No. 25860520 and No. 24390183 (to Otsuka M, Kishikawa T, Yoshikawa T and Koike K); Health Sciences Research Grants of The Ministry of Health, Labour and Welfare of Japan (to Koike K); Japanese Society of Gastroenterology, Okinaka Memorial Institute for Medical Research, and Honjo International Scholarship Foundation (to Otsuka M); Mishima Kaiun Memorial Foundation (to Ohno M); The Japan Prize Foundation and Tokyo Biomarker Innovation Research Association (to Kishikawa T).
Conflict-of-interest statement: The authors declare no competing financial interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Motoyuki Otsuka, MD, Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. otsukamo-tky@umin.ac.jp
Telephone: +81-3-38155411 Fax: +81-3-38140021
Received: January 3, 2015
Peer-review started: January 3, 2015
First decision: March 10, 2015
Revised: March 29, 2015
Accepted: June 15, 2015
Article in press: June 16, 2015
Published online: July 28, 2015
Abstract

Pancreatic cancer remains difficult to treat and has a high mortality rate. It is difficult to diagnose early, mainly due to the lack of screening imaging modalities and specific biomarkers. Consequently, it is important to develop biomarkers that enable the detection of early stage tumors. Emerging evidence is accumulating that tumor cells release substantial amounts of RNA into the bloodstream that strongly resist RNases in the blood and are present at sufficient levels for quantitative analyses. These circulating RNAs are upregulated in the serum and plasma of cancer patients, including those with pancreatic cancer, compared with healthy controls. The majority of RNA biomarker studies have assessed circulating microRNAs (miRs), which are often tissue-specific. There are few reports of the tumor-specific upregulation of other types of small non-coding RNAs (ncRNAs), such as small nucleolar RNAs and Piwi-interacting RNAs. Long ncRNAs (lncRNAs), such as HOTAIR and MALAT1, in the serum/plasma of pancreatic cancer patients have also been reported as diagnostic and prognostic markers. Among tissue-derived RNAs, some miRs show increased expression even in pre-cancerous tissues, and their expression profiles may allow for the discrimination between a chronic inflammatory state and carcinoma. Additionally, some miRs and lncRNAs have been reported with significant alterations in expression according to disease progression, and they may thus represent potential candidate diagnostic or prognostic biomarkers that may be used to evaluate patients once detection methods in peripheral blood are well established. Furthermore, recent innovations in high-throughput sequencing techniques have enabled the discovery of unannotated tumor-associated ncRNAs and tumor-specific alternative splicing as novel and specific biomarkers of cancers. Although much work is required to clarify the release mechanism, origin of tumor-specific circulating RNAs, and selectivity of carrier complexes, and technical advances must also be achieved, such as creating a consensus normalization protocol for quantitative data analysis, circulating RNAs are largely unexplored and might represent novel clinical biomarkers.

Keywords: MicroRNA, Non-coding RNA, Pancreatic cancer, Biomarkers, Early detection

Core tip: In this review, we summarize the latest findings on circulating RNAs in serum with a focus on their clinical use as novel diagnostic and prognostic biomarkers for pancreatic cancer. In addition, we summarize the current issues that need to be addressed to enable the clinical use of these circulating RNAs. This review will allow readers to concisely understand the current status and issues about the use of serum circulating RNAs as novel biomarkers for pancreatic cancer.