Open AccessHigh expression of the vacuole membrane protein 1 (VMP1) is a potential marker of poor prognosis in HER2 positive breast cancer
Author(s) -
Arsalan Amirfallah,
Aðalgeir Arason,
Hjörleifur Einarsson,
Eydis Thorunn Gudmundsdottir,
Edda S. Freysteinsdottir,
Katrín Ólafsdóttir,
Óskar Þór Jóhannsson,
Bjarni A. Agnarsson,
Rósa B. Barkardóttir,
Inga Reynisdóttir
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0221413
Subject(s) - cancer , breast cancer , protein expression , biology , vacuole , medicine , cancer research , genetics , gene , cytoplasm
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.