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      Integrated Transcriptome and Pathway Analyses Revealed Multiple Activated Pathways in Breast Cancer

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          Abstract

          Breast cancer (BC) is the leading cause of cancer-related death in women. Therefore, a better understanding of BC biology and signaling pathways might lead to the development of novel biomarkers and targeted therapies. Although a number of transcriptomic studies have been performed on breast cancer patients from various geographic regions, there are almost no such comprehensive studies performed on breast cancer from patients in the gulf region. This study aimed to provide a better understanding of the altered molecular networks in BC from the gulf region. Herein, we compared the transcriptome of BC to adjacent normal tissue from six BC patients and identified 1,108 upregulated and 518 downregulated transcripts. A selected number of genes from the RNA-Seq analysis were subsequently validated using qRT-PCR. Differentially expressed (2.0-fold change, adj. p < 0.05) transcripts were subjected to ingenuity pathway analysis, which revealed a myriad of affected signaling pathways and functional categories. Activation of ERBB2, FOXM1, ESR1, and IGFBP2 mechanistic networks was most prominent in BC tissue. Additionally, BC tissue exhibited marked enrichment in genes promoting cellular proliferation, migration, survival, and DNA replication and repair. The presence of genes indicative of immune cell infiltration and activation was also observed in BC tissue. We observed high concordance [43.5% (upregulated) and 62.1% (downregulated)] between differentially expressed genes in our study group and those reported for the TCGA BC cohort. Our data provide novel insight on BC biology and suggest common altered molecular networks in BC in this geographic region. Our data suggest future development of therapeutic interventions targeting those common signaling pathways.

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          A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer.

          We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (P(trend) for the most strongly associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci.
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            Chemokines and Chemokine Receptors: New Targets for Cancer Immunotherapy

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              Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers

              Effective management of breast cancer depends on early diagnosis and proper monitoring of patients’ response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising biomarker, given the ease with which miRNAs can be isolated and their structural stability under different conditions of sample processing and isolation. In this review, we provide current state-of-the-art of miRNA biogenesis, function and discuss the advantages, limitations, as well as pitfalls of using circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management.
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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
                18 September 2019
                2019
                : 9
                : 910
                Affiliations
                Cancer Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation , Doha, Qatar
                Author notes

                Edited by: Ala-Eddin Al Moustafa, Qatar University, Qatar

                Reviewed by: Hamid Morjani, Université de Reims Champagne-Ardenne, France; Luigi Fattore, Sapienza University of Rome, Italy

                *Correspondence: Eyad Elkord eelkord@ 123456hbku.edu.qa

                This article was submitted to Molecular and Cellular Oncology, a section of the journal Frontiers in Oncology

                †These authors have contributed equally to this work

                Article
                10.3389/fonc.2019.00910
                6759650
                31620367
                24aeb7d8-8b40-4e91-947f-1343bd84a42b
                Copyright © 2019 Vishnubalaji, Sasidharan Nair, Ouararhni, Elkord and Alajez.

                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
                : 03 June 2019
                : 02 September 2019
                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 47, Pages: 13, Words: 6415
                Funding
                Funded by: Qatar Foundation 10.13039/100007458
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                breast cancer,rna-seq,pathway analysis,transcriptome,ipa
                Oncology & Radiotherapy
                breast cancer, rna-seq, pathway analysis, transcriptome, ipa

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