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      Overexpression of ASPM, CDC20, and TTK Confer a Poorer Prognosis in Breast Cancer Identified by Gene Co-expression Network Analysis

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          Abstract

          Breast cancer is one of the most common malignancies among females, and its prognosis is affected by a complex network of gene interactions. In this study, we constructed free-scale gene co-expression networks using weighted gene co-expression network analysis (WGCNA). The gene expression profiles of GSE25055 were downloaded from the Gene Expression Omnibus (GEO) database to identify potential biomarkers associated with breast cancer progression. GSE42568 was downloaded for validation. A total of 9 modules were established via the average linkage hierarchical clustering. We identified 3 hub genes (ASPM, CDC20, and TTK) in the significant module ( R 2 = 0.52), which were significantly correlated with poor prognosis both in test and validation datasets. In the datasets GSE25055 and GSE42568, higher expression levels of ASPM, CDC20, and TTK correlated with advanced tumor grades. Immunohistochemistry data from the Human Protein Atlas also demonstrated that their protein levels were higher in tumor samples. According to gene set enrichment analysis, 4 commonly enriched pathways were identified: cell cycle pathway, DNA replication pathway, homologous recombination pathway, and P53 signaling pathway. In addition, strong correlations were found among their expression levels. In conclusion, our WGCNA analysis identified candidate prognostic biomarkers for further basic and clinical researches.

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          Most cited references28

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          Concordance among gene-expression-based predictors for breast cancer.

          Gene-expression-profiling studies of primary breast tumors performed by different laboratories have resulted in the identification of a number of distinct prognostic profiles, or gene sets, with little overlap in terms of gene identity. To compare the predictions derived from these gene sets for individual samples, we obtained a single data set of 295 samples and applied five gene-expression-based models: intrinsic subtypes, 70-gene profile, wound response, recurrence score, and the two-gene ratio (for patients who had been treated with tamoxifen). We found that most models had high rates of concordance in their outcome predictions for the individual samples. In particular, almost all tumors identified as having an intrinsic subtype of basal-like, HER2-positive and estrogen-receptor-negative, or luminal B (associated with a poor prognosis) were also classified as having a poor 70-gene profile, activated wound response, and high recurrence score. The 70-gene and recurrence-score models, which are beginning to be used in the clinical setting, showed 77 to 81 percent agreement in outcome classification. Even though different gene sets were used for prognostication in patients with breast cancer, four of the five tested showed significant agreement in the outcome predictions for individual patients and are probably tracking a common set of biologic phenotypes. Copyright 2006 Massachusetts Medical Society.
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            Breast cancer as a systemic disease: a view of metastasis.

            Breast cancer is now the most frequently diagnosed cancer and leading cause of cancer death in women worldwide. Strategies targeting the primary tumour have markedly improved, but systemic treatments to prevent metastasis are less effective; metastatic disease remains the underlying cause of death in the majority of patients with breast cancer who succumb to their disease. The long latency period between initial treatment and eventual recurrence in some patients suggests that a tumour may both alter and respond to the host systemic environment to facilitate and sustain disease progression. Results from studies in animal models suggest that specific subtypes of breast cancer may direct metastasis through recruitment and activation of haematopoietic cells. In this review, we focus on data implicating breast cancer as a systemic disease. © 2013 The Association for the Publication of the Journal of Internal Medicine.
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              Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial.

              The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                24 April 2019
                2019
                : 9
                : 310
                Affiliations
                [1] 1Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University , Wuhan, China
                [2] 2Department of Urology, Zhongnan Hospital of Wuhan University , Wuhan, China
                [3] 3Department of Thyroid and Breast Surgery, Tongji Hospital, Huazhong University of Science and Technology , Wuhan, China
                [4] 4Department of General Surgery, Zhongnan Hospital of Wuhan University , Wuhan, China
                [5] 5Department of Biological Repositories, Zhongnan Hospital of Wuhan University , Wuhan, China
                Author notes

                Edited by: Subha Madhavan, Georgetown University, United States

                Reviewed by: Jian Zhu, UT Southwestern Medical Center, United States; Saori Furuta, University of Toledo, United States

                *Correspondence: Yan Gong yan.gong@ 123456whu.edu.cn

                This article was submitted to Women's Cancer, a section of the journal Frontiers in Oncology

                †These authors have contributed equally to this work

                Article
                10.3389/fonc.2019.00310
                6492458
                31106147
                1d5fb5b8-c44d-47c8-88b7-feb11b217e2b
                Copyright © 2019 Tang, Lu, Cui, Zhang, Kong, Liao, Ren, Gong and Wu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 December 2018
                : 05 April 2019
                Page count
                Figures: 11, Tables: 0, Equations: 2, References: 40, Pages: 14, Words: 5642
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                breast cancer,wgcna,aspm,cdc20,ttk,prognosis
                Oncology & Radiotherapy
                breast cancer, wgcna, aspm, cdc20, ttk, prognosis

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