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Tytuł:
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Investigation of genes and pathways involved in breast cancer subtypes through gene expression meta-analysis.
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Autorzy:
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Jafarinejad-Farsangi S; Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: .
Moazzam-Jazi M; Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: .
Naderi Ghale-Noie Z; Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: .
Askari N; Department of Biotechnology, Institute of Sciences and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran. Electronic address: .
Miri Karam Z; Student Research Center, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: .
Mollazadeh S; Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran. Electronic address: .
Hadizadeh M; Student Research Center, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: .
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Źródło:
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Gene [Gene] 2022 May 05; Vol. 821, pp. 146328. Date of Electronic Publication: 2022 Feb 16.
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Typ publikacji:
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Journal Article; Meta-Analysis
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Język:
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English
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Imprint Name(s):
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Original Publication: Amsterdam, Elsevier/North-Holland, 1976-
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MeSH Terms:
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Gene Regulatory Networks*
Breast Neoplasms/*classification
Gene Expression Profiling/*methods
Breast Neoplasms/genetics ; Databases, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; Sequence Analysis, RNA
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Contributed Indexing:
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Keywords: Breast cancer; Breast cancer subtypes; Gene expression meta-analysis; Microarray
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Entry Date(s):
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Date Created: 20220219 Date Completed: 20220318 Latest Revision: 20220318
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Update Code:
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20240105
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DOI:
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10.1016/j.gene.2022.146328
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PMID:
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35181505
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Background: Molecular-based studies have revealed heterogeneity in Breast cancer BC while also improving classification and treatment. However, efforts are underway to distinguish between distinct subtypes of breast cancer. In this study, the results of several microarray studies were combined to identify genes and pathways specific to each BC subtype.
Methods: Meta-analysis of multiple gene expression profile datasets was screened to find differentially expressed genes (DEGs) across subtypes of BC and normal breast tissue samples. Protein-protein interaction network and gene set enrichment analysis were used to identify critical genes and pathways associated with BC subtypes. The differentially expressed genes from meta-analysis was validated using an independent comprehensive breast cancer RNA-sequencing dataset obtained from the Cancer Genome Atlas (TCGA).
Results: We identified 110 DEGs (13 DEGs in all and 97 DEGs in each subtype) across subtypes of BC. All subtypes had a small set of shared DEGs enriched in the Chemokine receptor bind chemokine pathway. Luminal A specific were enriched in the translational elongation process in mitochondria, and the enhanced process in luminal B subtypes was interferon-alpha/beta signaling. Cell cycle and mitotic DEGs were enriched in the basal-like group. All subtype-specific DEG genes (100%) were successfully validated for Luminal A, Luminal B, ERBB2, and Normal-like. However, the validation percentage for Basal-like group was 77.8%.
Conclusion: Integrating researches such as a meta-analysis of gene expression might be more effective in uncovering subtype-specific DEGs and pathways than a single-study analysis. It would be more beneficial to increase the number of studies that use matched BC subtypes along with GEO profiling approaches to reach a better result regarding DEGs and reduce probable biases. However, achieving 77.8% overlap in basal-specific genes and complete concordance in specific genes related to other subtypes can implicate the strength of our analysis for discovering the subtype-specific genes.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
