Abstract
Homeobox (HOX) family genes encode key transcription factors for embryogenesis and may be correlated with carcinogenesis. The aim of this study was to elucidate whether aberrant expression of HOX genes influences outcomes in epithelial ovarian cancer (EOC). Gene expression data and clinicopathologic information from 630 patients with EOC were downloaded from The Cancer Genome Atlas database. We explored correlations between expression levels of HOX gene family members and clinicopathological variables. Higher expression of HOXA1, A4, A5, A7, A10, A11, B13, C13, D1, and D3 was associated with advanced FIGO stage. Suboptimal residual disease after debulking surgery was significantly correlated with higher expression of HOXB9, B13, and C13. Additionally, patients with high expression of HOXC6 and C11 were significantly more likely to have poor performance status. Overall survival was significantly shorter in patients with high, rather than low, expression of two HOX genes (HOXA10 and B3), and significantly longer in patients with high rather than low HOXC5 expression. Dysregulated expression of the HOXA10, B3, and C5 was significantly correlated with overall survival in EOC patients. HOX gene expression levels are potentially useful as a prognostic indicator in EOC, and HOX genes may represent a novel and promising target for anticancer therapeutics.
Highlights
Epithelial ovarian cancer (EOC), the leading cause of gynecologic cancer-related mortality, is known to be a multifactorial disease involving genetic, environmental, and epigenetic factors [1, 2]
Previous studies showed that dysregulation of several HOX genes was associated with adverse prognostic factors in epithelial ovarian cancer (EOC); the majority of this research was limited by small sample sizes and was performed only in vitro [8,9,10,11,12,13,14]
We demonstrated that increased mRNA expression of certain HOX genes was independently associated with multiple risk factors, including advanced Federation of Gynecology and Obstetrics (FIGO) stage, suboptimal residual disease, and poor performance status, that were found to influence survival outcomes in ovarian cancer using the The Cancer Genome Atlas (TCGA) database
Summary
Epithelial ovarian cancer (EOC), the leading cause of gynecologic cancer-related mortality, is known to be a multifactorial disease involving genetic, environmental, and epigenetic factors [1, 2]. Homeobox (HOX) genes, defined by a highly conserved 183-base pair DNA sequence called the homeobox, encode homeoproteins that function as transcription factors in differentiation and proliferation processes during embryonic structural development [4]. Aberrant expression of these proteins has been associated with carcinogenesis and aggressiveness [5, 6]. Several studies have shown potential roles for HOX antisense long non-coding RNAs in ovarian cancer aggressiveness [15, 16] These results suggest that aberrant www.impactjournals.com/oncotarget expression of HOX genes may be correlated with the process of ovarian cancer carcinogenesis
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