title: Circulating RNAs as new biomarkers for detecting pancreatic cancer.
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.
authors.affiliation: 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.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kishikawa
authors.affiliation: 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.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.affiliation: 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.
authors.forename: Motoko
authors.initials: M
authors.lastname: Ohno
authors.affiliation: 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.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: 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.
authors.forename: Akemi
authors.initials: A
authors.lastname: Takata
authors.affiliation: 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.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods*; D006801:Humans; D025202:Molecular Diagnostic Techniques; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D012313:RNA / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D022661:RNA, Untranslated / Q000097:blood / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D022661:RNA, Untranslated; D012313:RNA
keywords: Biomarkers; Early detection; MicroRNA; Non-coding RNA; Pancreatic cancer