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High expression of ZNF703 independent of amplification indicates worse prognosis in patients with luminal B breast cancer.

ABSTRACT: Amplification of 8p12-p11 is relatively common in breast cancer and several genes within the region have been suggested to affect breast tumor progression. The aim of the study was to map the amplified 8p12-p11 region in a large set of breast tumors in an effort to identify the genetic driver and to explore its impact on tumor progression and prognosis. Copy number alterations (CNAs) were mapped in 359 tumors, and gene expression data from 577 tumors (359 tumors included) were correlated with CNA, clinical-pathological factors, and protein expression (39 tumors). 8p12-p11 was amplified in 11.4% of tumors. The smallest region of amplification harbored one full-length gene, ZNF703. ZNF703 mRNA expression was significantly higher in estrogen receptor (ER)-positive than ER-negative tumors (P = 2 × 10(-16)), a reflection of high expression in luminal tumors. Forty-eight percent of tumors with ZNF703 amplification were luminal B tumors in which the best correlation between DNA copy number and mRNA was seen (P = 1.2 × 10(-7)) as well as correlation between mRNA and protein expression (P = 0.02). High ZNF703 mRNA correlated with poor survival in patients with ER-positive luminal B tumors (log rank P = 0.04). Furthermore, high ZNF703 mRNA expression correlated with poor outcome in patients with ZNF703 copy number neutral, ER-positive, luminal B tumors (log rank P = 0.004). The results support ZNF703 as the driver gene of the 8p12 amplification and suggest that independent of amplification, high expression of the gene affects prognosis in luminal B tumors.

SUBMITTER: Reynisdottir I

PROVIDER: S-EPMC3799278 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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High expression of ZNF703 independent of amplification indicates worse prognosis in patients with luminal B breast cancer.

Reynisdottir Inga I Arason Adalgeir A Einarsdottir Berglind O BO Gunnarsson Haukur H Staaf Johan J Vallon-Christersson Johan J Jonsson Goran G Ringnér Markus M Agnarsson Bjarni A BA Olafsdottir Kristrun K Fagerholm Rainer R Einarsdottir Thorbjorg T Johannesdottir Gudrun G Johannsson Oskar Thor OT Nevanlinna Heli H Borg Ake A Barkardottir Rosa Bjork RB

Cancer medicine 20130522 4

Amplification of 8p12-p11 is relatively common in breast cancer and several genes within the region have been suggested to affect breast tumor progression. The aim of the study was to map the amplified 8p12-p11 region in a large set of breast tumors in an effort to identify the genetic driver and to explore its impact on tumor progression and prognosis. Copy number alterations (CNAs) were mapped in 359 tumors, and gene expression data from 577 tumors (359 tumors included) were correlated with CN ...[more]

PMID: 24156016

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Project description:BackgroundEpithelial-mesenchymal transition (EMT) plays a crucial role in the progression and aggressiveness of colorectal carcinoma. E-cadherin is the best-characterized molecular marker of EMT, but its prognostic significance for patients with CRC remains inconclusive.MethodologyEligible studies were searched from the PubMed, Embase and Web of Science databases. Correlation between E-cadherin expression and clinicopathological features and prognosis was analyzed. Subgroup analysis was also performed according to study location, number of patients, quality score of studies and cut-off value.Principal findingsA total of 27 studies comprising 4244 cases met the inclusion criteria. Meta-analysis suggested that downregulated E-cadherin expression had an unfavorable impact on overall survival (OS) of CRC (n?=?2730 in 14 studies; HR?=?2.27, 95%CI: 1.63-3.17; Z?=?4.83; P?=?0.000). Subgroup analysis indicated that low E-cadherin expression was significantly associated with worse OS in Asian patients (n?=?1054 in 9 studies; HR?=?2.86, 95%CI: 2.13-3.7, Z?=?7.11; P?=?0.000) but not in European patients (n?=?1552 in 4 studies; HR?=?1.14, 95%CI: 0.95-1.35, Z?=?1.39; P?=?0.165). In addition, reduced E-cadherin expression indicated an unfavorable OS only when the cut off value of low E-cadherin expression was >50% (n?=?512 in 4 studies; HR?=?2.08, 95%CI 1.45-2.94, Z?=?4.05; P?=?0.000). Downregulated E-cadherin expression was greatly related with differentiation grade, Dukes' stages, lymphnode status and metastasis. The pooled OR was 0.36(95%CI: 0.19-0.7, Z?=?3.03, P?=?0.002), 0.34(95%CI: 0.21-0.55, Z?=?6.61, P?=?0.000), 0.49(95%CI: 0.32-0.74, Z?=?3.02, P?=?0.002) and 0.45(95%CI: 0.22-0.91, Z?=?3.43, P?=?0.001), respectively.ConclusionsThis study showed that low or absent E-cadherin expression detected by immunohistochemistry served as a valuable prognostic factor of CRC. However, downregulated E-cadherin expression seemed to be associated with worse prognosis in Asian CRC patients but not in European CRC patients. Additionally, this meta-analysis suggested that the negative threshold of E-cadherin should be >50% when we detected its expression in the immunohistochemistry stain.

Dataset Information

High expression of ZNF703 independent of amplification indicates worse prognosis in patients with luminal B breast cancer.

Publications

High expression of ZNF703 independent of amplification indicates worse prognosis in patients with luminal B breast cancer.

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