Universität zu Köln

Plum, Patrick Sven, Warnecke-Eberz, Ute, Drebber, Uta, Chon, Seung-Hun ORCID: 0000-0002-8923-6428, Alakus, Hakan, Hoelscher, Arnulf Heinrich, Quaas, Alexander, Bruns, Christiane Josephine, Gockel, Ines, Lorenz, Dietmar, Metzger, Ralf and Bollschweiler, Elfriede (2019). Upregulation of miR-17-92 cluster is associated with progression and lymph node metastasis in oesophageal adenocarcinoma. Sci Rep, 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

The occurrence of lymph node metastasis (LNM) and depth of tumour infiltration are significant prognostic factors in oesophageal adenocarcinoma (OAC), however no reliable prognostic biomarkers have been established so far. Aim of this study was to characterize microRNAs (miRs) of OAC patients, who primarily underwent oesophagectomy, in order to identify specific alterations during tumour progression and LNM. MicroRNA array-based quantification analysis of 754 miRs, including tumour specimens of 12 patients with pT2 OAC from three different centres (detection group), was performed. We identified miR-17, miR-19a/b, miR-20a, and miR-106a, showing the best predictive power for LNM. These miRs were validated by quantitative real time-PCR (qRT-PCR) in 43 patients with different tumour stages (pT1: n = 21; pT2: n = 12 and pT3: n = 10) (training group) (p < 0.05), demonstrating that increasing levels of identified miRs were associated with advanced depth of tumour infiltration. These findings were verified in another independent group of 46 pT2 OAC patients (validation group). Quantitative RT-PCR analysis of the miR-panel confirmed these results except for miR-19a (p < 0.05 each). Logistic regression analysis identified miR-17 and miR-20a (p = 0.025 and p = 0.022, respectively) to be independent variables for prediction of LNM. The mathematical prediction model was used in the validation group, and the estimated prognosis was compared to the actual postsurgical follow-up. This comprehensive data demonstrated the importance of miR-17-92 cluster and miR-106a for progression as well as LNM in OAC indicating that those might be feasible prognostic biomarkers.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Plum, Patrick Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Warnecke-Eberz, Ute UNSPECIFIED UNSPECIFIED UNSPECIFIED Drebber, Uta UNSPECIFIED UNSPECIFIED UNSPECIFIED Chon, Seung-Hun UNSPECIFIED orcid.org/0000-0002-8923-6428 UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoelscher, Arnulf Heinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane Josephine UNSPECIFIED UNSPECIFIED UNSPECIFIED Gockel, Ines UNSPECIFIED UNSPECIFIED UNSPECIFIED Lorenz, Dietmar UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzger, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Bollschweiler, Elfriede UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-144109
DOI:	10.1038/s41598-019-48624-0
Journal or Publication Title:	Sci Rep
Volume:	9
Date:	2019
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BARRETTS-ESOPHAGUS; CANCER; MICRORNAS; TRENDS; IMPACT; EXPRESSION; SIGNATURES; DIAGNOSIS; INVASION; PLASMA Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14410