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DCYTB is a predictor of outcome in breast cancer that functions via iron-independent mechanisms.

ABSTRACT: BACKGROUND:Duodenal cytochrome b (DCYTB) is a ferrireductase that functions together with divalent metal transporter 1 (DMT1) to mediate dietary iron reduction and uptake in the duodenum. DCYTB is also a member of a 16-gene iron regulatory gene signature (IRGS) that predicts metastasis-free survival in breast cancer patients. To better understand the relationship between DCYTB and breast cancer, we explored in detail the prognostic significance and molecular function of DCYTB in breast cancer. METHODS:The prognostic significance of DCYTB expression was evaluated using publicly available microarray data. Signaling Pathway Impact Analysis (SPIA) of microarray data was used to identify potential novel functions of DCYTB. The role of DCYTB was assessed using immunohistochemistry and measurements of iron uptake, iron metabolism, and FAK signaling. RESULTS:High DCYTB expression was associated with prolonged survival in two large independent cohorts, together totaling 1610 patients (cohort #1, p?=?1.6e-11, n?=?741; cohort #2, p?=?1.2e-05, n?=?869; log-rank test) as well as in the Gene expression-based Outcome for Breast cancer Online (GOBO) cohort (p?

SUBMITTER: Lemler DJ

PROVIDER: S-EPMC5341190 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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DCYTB is a predictor of outcome in breast cancer that functions via iron-independent mechanisms.

Lemler David J DJ Lynch Miranda L ML Tesfay Lia L Deng Zhiyong Z Paul Bibbin T BT Wang Xiaohong X Hegde Poornima P Manz David H DH Torti Suzy V SV Torti Frank M FM

Breast cancer research : BCR 20170307 1

<h4>Background</h4>Duodenal cytochrome b (DCYTB) is a ferrireductase that functions together with divalent metal transporter 1 (DMT1) to mediate dietary iron reduction and uptake in the duodenum. DCYTB is also a member of a 16-gene iron regulatory gene signature (IRGS) that predicts metastasis-free survival in breast cancer patients. To better understand the relationship between DCYTB and breast cancer, we explored in detail the prognostic significance and molecular function of DCYTB in breast c ...[more]

PMID: 28270217

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Project description:BackgroundZNF385B, a zinc finger protein, has been known as a potential biomarker in some neurological and hematological studies recently. Although numerous studies have demonstrated the potential function of zinc finger proteins in tumor progression, the effects of ZNF385B in breast cancer (BC) are less studied.MethodsThe Oncomine database and "ESurv" tool were used to explore the differential expression of ZNF385B in pan-cancer. Furthermore, data of patients with BC were downloaded from The Cancer Genome Atlas (TCGA). The receiver operating characteristic (ROC) curve of ZNF385B expression was established to explore the diagnostic value of ZNF385B and to obtain the cut-off value of high or low ZNF385B expression in BC. The chi-square test as well as Fisher exact test was used for identification of the relationships between clinical features and ZNF385B expression. Furthermore, the effects of ZNF385B on BC patients' survival were evaluated by the Kaplan-Meier and Cox regression. Data from the Gene Expression Omnibus (GEO) database were employed to validate the results of TCGA. Protein expression of ZNF385B in BC patient specimens was detected by immunohistochemistry (IHC) staining.ResultsZNF385B expression was downregulated in most types of cancer including BC. Low ZNF385B expression was related with survival status, overall survival (OS), and recurrence of BC. ZNF385B had modest diagnostic value, which is indicated by the area under the ROC curve (AUC = 0.671). Patients with lower ZNF385B expression had shorter OS and RFS (relapse-free survival). It had been demonstrated that low ZNF385B expression represented independent prognostic value for OS and RFS by multivariate survival analysis. The similar results were verified by datasets from the GEO database as well. The protein expression of ZNF385B was decreased in patients' samples compared with adjacent tissues by IHC.ConclusionsLow ZNF385B expression was an independent predictor for worse prognosis of BC patients.

Dataset Information

DCYTB is a predictor of outcome in breast cancer that functions via iron-independent mechanisms.

Publications

DCYTB is a predictor of outcome in breast cancer that functions via iron-independent mechanisms.

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