Abstract
Ovarian cancer (OC) metastasis presents major hurdles that must be overcome to improve patient outcomes. Recent studies have demonstrated copy number variations (CNVs) frequently contribute to alterations in oncogenic drivers. The present study used a CytoScan HD Array to analyse CNVs and loss of heterozygosity (LOH) in the entire genomes of 6 OC patients and human OC cell lines to determine the genetic target events leading to the distinct invasive/migratory capacities of OC. The results showed that LOH at Xq11.1 and Xp21.1 and gains at 8q21.13 were novel, specific CNVs. Ovarian cancer-related CNVs were then screened by bioinformatics analysis. In addition, transcription factors-target gene interactions were predicted with information from PASTAA analysis. As a result, six genes (i.e., GAB2, AKT1, EGFR, COL6A3, UGT1A1 and UGT1A8) were identified as strong candidates by integrating the above data with gene expression and clinical outcome data. In the transcriptional regulatory network, 4 known cancer-related transcription factors (TFs) interacted with 6 CNV-driven genes. The protein/DNA arrays revealed 3 of these 4 TFs as potential candidate gene-related transcription factors in OC. We then demonstrated that these six genes can serve as potential biomarkers for OC. Further studies are required to elucidate the pathogenesis of OC.
Highlights
Ovarian cancer (OC) is a deadly disease that affects women globally
The most common Copy number variations (CNVs) regions in the OC samples compared with the normal samples involved both loss of heterozygosity (LOH) regions, including Xq11.1 and Xp21.1, and amplifications, including 8q21.13, 8q11.21, and 8q23.3
The results showed that high GAB2, AKT1, EGFR, and COL6A3 expression were associated with poor Progression-free survival (PFS) for OC patients (P
Summary
Ovarian cancer (OC) is a deadly disease that affects women globally. The worldwide incidence of OC is currently 225,500 new diagnoses each year [1,2]. Highgrade OC generally grows rapidly, metastasizes early, and has a very aggressive disease course and high rate of chemotherapy resistance [3]. A growing number of studies have reported that CNVs are correlated with the genetic and phenotypic diversity of tumours and are frequently associated with the activation of oncogenic drivers or the deletion of tumour suppressor factors [6,7,8,9]. Previous studies using either conventional metaphase chromosome-based comparative genomic hybridization [10,11] or array-based high-resolution genomic technology to identify genome-wide CNVs in OC [12,13,14,15,16,17,18,19] have identified regions of frequently increased copy number along chromosomes 1, 3, 7, 8, 17 and 20 and reduced copy number along chromosomes 1, www.aging-us.com
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