Abstract
BackgroundThe dyslexia candidate gene, DYX1C1, shown to regulate and interact with estrogen receptors and involved in the regulation of neuronal migration, has recently been proposed as a putative cancer biomarker. This study was undertaken to assess the prognostic value and therapy-predictive potential of DYX1C1 mRNA and protein expression in breast cancer.MethodsDYX1C1 mRNA expression was assessed at the mRNA level in three independent population-derived patient cohorts. An association to estrogen/progesterone receptor status, Elston grade, gene expression subtype and lymph node status was analyzed within these cohorts. DYX1C1 protein expression was examined using immunohistochemistry in cancer and normal breast tissue. The statistical analyses were performed using the non-parametric Wilcoxon rank-sum test, ANOVA, Fisher's exact test and a multivariate proportional hazard (Cox) model.ResultsDYX1C1 mRNA is significantly more highly expressed in tumors that have been classified as estrogen receptor α and progesterone receptor-positive. The expression of DYX1C1 among the molecular subtypes shows the lowest median expression within the basal type tumors, which are considered to have the worst prognosis. The expression of DYX1C1 is significantly lower in tumors graded as Elston grade 3 compared with grades 1 and 2. DYX1C1 protein is expressed in 88% of tumors and in all 10 normal breast tissues examined. Positive protein expression was significantly correlated to overall survival (Hazard ratio 3.44 [CI 1.84-6.42]) of the patients but not to any of the variables linked with mRNA expression.ConclusionWe show that the expression of DYX1C1 in breast cancer is associated with several clinicopathological parameters and that loss of DYX1C1 correlates with a more aggressive disease, in turn indicating that DYX1C1 is a potential prognostic biomarker in breast cancer.
Highlights
The dyslexia candidate gene, dyslexia susceptibility 1 candidate 1 (DYX1C1), shown to regulate and interact with estrogen receptors and involved in the regulation of neuronal migration, has recently been proposed as a putative cancer biomarker
We examined the differences in DYX1C1 expression in two independent breast cancer patient cohorts, from Uppsala and Stockholm, where transcriptome gene expression microarrays had been performed
Our results indicate that DYX1C1 mRNA is more highly expressed in ERa-positive or progesterone receptor (PR)-positive breast cancer tumors
Summary
The dyslexia candidate gene, DYX1C1, shown to regulate and interact with estrogen receptors and involved in the regulation of neuronal migration, has recently been proposed as a putative cancer biomarker. This study was undertaken to assess the prognostic value and therapy-predictive potential of DYX1C1 mRNA and protein expression in breast cancer. Breast cancer is a heterogeneous disease consisting of several distinct subtypes with characteristic gene expression patterns resulting in differences in overall survival [1,2]. Kim et al proposed dyslexia susceptibility 1 candidate 1 (DYX1C1) as a potential cancer biomarker after comparing splice variant-specific RNA levels in a variety of different human tumors and normal samples [7]. DYX1C1 has been shown to interact with the intracellular chaperones Hsp, Hsp, and the ubiquination ligase CHIP [10,11]. When overexpressed in the SH-SY5Y line, DYX1C1 interacts with and regulates both the levels of ERa as well as the second estrogen receptor, ESR2 (ERb) in a dose-dependent fashion, likely through an interaction with CHIP [12]
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