dc.contributor |
Háskóli Íslands |
dc.contributor |
University of Iceland |
dc.contributor.author |
Amirfallah, Arsalan |
dc.contributor.author |
Arason, Adalgeir |
dc.contributor.author |
Einarsson, Hjörleifur |
dc.contributor.author |
Guðmundsdóttir, Eydís Þórunn |
dc.contributor.author |
Freysteinsdóttir, Edda Sigríður |
dc.contributor.author |
Ólafsdóttir, Kristrún Auður |
dc.contributor.author |
Jóhannsson, Óskar Þór |
dc.contributor.author |
Agnarsson, Bjarni A. |
dc.contributor.author |
Barkardottir, Rosa Bjork |
dc.contributor.author |
Reynisdottir, Inga |
dc.date.accessioned |
2020-08-10T10:43:58Z |
dc.date.available |
2020-08-10T10:43:58Z |
dc.date.issued |
2019-08-23 |
dc.identifier.citation |
Amirfallah A, Arason A, Einarsson H, Gudmundsdottir ET, Freysteinsdottir ES, Olafsdottir KA, et al. (2019) High expression of the vacuole membrane protein 1 (VMP1) is a potential marker of poor prognosis in HER2 positive breast cancer. PLoS ONE 14(8): e0221413. https://doi.org/10.1371/journal.pone.0221413 |
dc.identifier.issn |
1932-6203 |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/1941 |
dc.description |
Publisher's version (útgefin grein) |
dc.description.abstract |
Background: Fusion genes result from genomic structural changes, which can lead to alterations in gene expression that supports tumor development. The aim of the study was to use fusion genes as a tool to identify new breast cancer (BC) genes with a role in BC progression.
Methods: Fusion genes from breast tumors and BC cell lines were collected from publications. RNA-Seq data from tumors and cell lines were retrieved from databanks and analyzed for fusions with SOAPfuse or the analysis was purchased. Fusion genes identified in both tumors (n = 1724) and cell lines (n = 45) were confirmed by qRT-PCR and sequencing. Their individual genes were ranked by selection criteria that included correlation of their mRNA level with copy number. The expression of the top ranked gene was measured by qRT-PCR in normal tissue and in breast tumors from an exploratory cohort (n = 141) and a validation cohort (n = 277). Expression levels were correlated with clinical and pathological factors as well as the patients’ survival. The results were followed up in BC cohorts from TCGA (n = 818) and METABRIC (n = 2509).
Results: Vacuole membrane protein 1 (VMP1) was the most promising candidate based on specific selection criteria. Its expression was higher in breast tumor tissue than normal tissue (p = 1x10-4), and its expression was significantly higher in HER2 positive than HER2 negative breast tumors in all four cohorts analyzed. High expression of VMP1 associated with breast cancer specific survival (BCSS) in cohort 1 (hazard ratio (HR) = 2.31, CI 1.27–4.18) and METABRIC (HR = 1.26, CI 1.02–1.57), and also after adjusting for HER2 expression in cohort 1 (HR = 2.03, CI 1.10–3.72). BCSS was not significant in cohort 2 or TCGA cohort, which may be due to differences in treatment regimens.
Conclusions: The results suggest that high VMP1 expression is a potential marker of poor prognosis in HER2 positive BC. Further studies are needed to elucidate how VMP1 could affect pathways supportive of tumorigenesis. |
dc.description.sponsorship |
This work was supported by a grant to IR, RBB, BAA, OTJ and Ad Ar from The Icelandic Centre for Research Fund (152530-051, www.rannis.is), to IR, RBB, BAA and OTJ from The Scientific Fund of Landspitali – The National University Hospital in Iceland (A-2015-039, A-2018-034, www.landspitali.is), and grants from Gongum saman (2013 and 2017 to IR and RBB, and 2018 to Ar Am, http://www.gongumsaman.is/). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
dc.format.extent |
e0221413 |
dc.language.iso |
en |
dc.publisher |
Public Library of Science (PLoS) |
dc.relation.ispartofseries |
Plos One;14(8) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
VMP1 |
dc.subject |
Breast cancer |
dc.subject |
Tumor |
dc.subject |
Brjóstakrabbamein |
dc.subject |
Genarannsóknir |
dc.title |
High expression of the vacuole membrane protein 1 (VMP1) is a potential marker of poor prognosis in HER2 positive breast cancer |
dc.type |
info:eu-repo/semantics/article |
dcterms.license |
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
dc.description.version |
Peer Reviewed |
dc.identifier.journal |
Plos One |
dc.identifier.doi |
10.1371/journal.pone.0221413 |
dc.relation.url |
http://dx.plos.org/10.1371/journal.pone.0221413 |
dc.contributor.department |
Lífvísindasetur (HÍ) |
dc.contributor.department |
Biomedical Center (UI) |
dc.contributor.department |
Læknadeild (HÍ) |
dc.contributor.department |
Faculty of Medicine (UI) |
dc.contributor.school |
Heilbrigðisvísindasvið (HÍ) |
dc.contributor.school |
School of Health Sciences (UI) |