• A systems biology approach for analysis important genes related to glycolysis pathway in Triple Negative Breast Cancer
  • Majdedin Ghalavand,1 Samira Mohammadi Yeganeh,2,* Ruhollah Dorostkar,3 Azar Moradi,4 Seyed Mahmoud Hashemi,5
    1. 1. Student Research Committee, Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Department of Biotechnology, School of Advanced Technology in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    2. 2. Department of Biotechnology, School of Advanced Technology in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    3. 4. Applied Virology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
    4. 1. Student Research Committee, Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Department of Biotechnology, School of Advanced Technology in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    5. 5. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran


  • Introduction: Triple-negative breast cancer (TNBC) lack expression of the estrogen receptor (ER), the progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Compared with the other breast cancer subtypes, TNBCs tend to occur at a younger age and have a higher rate of reoccurrence and worse outcomes. Because ER, PR, and HER2 are lacking, no targeted therapies are currently available for TNBC, and treatment options are restricted to surgery, radiation therapy, and chemotherapy. Approximately 15–20% of all breast cancers are triple-negative, and about 75% of TNBCs also fall into the basal subclass of breast cancer, which is defined by a gene-expression signature. The aggressiveness of TNBC and the lack of targeted therapies highlight the need to understand the pathways required for TNBC growth and survival. Glycolysis is the process in which one glucose molecule is broken down to form two molecules of pyruvic acid. The glycolysis process is a multi-step metabolic pathway that occurs in the cytoplasm of animal cells, plant cells, and the cells of microorganisms. The essential metabolic pathway of glycolysis involves the oxidative breakdown of one glucose into two pyruvates with the capture of some energy as ATP and NADH. Glycolysis is important in the cell because glucose is the main source of fuel for tissues in the body. The main purpose of glycolysis is to provide pyruvate for the trichloroacetic acid (TCA) cycle. Cancer cells up-regulate glucose and glutamine metabolism to fuel their bioenergetic and biosynthetic demands. TNBC is aggressive and lacks targeted therapies, having elevated glucose uptake and a glycolytic gene-expression signature, therefore Understanding how nutrients are used in TNBCs may provide new targets for therapeutic intervention. The aim of study was to analysis important genes involved in the glycolysis pathway of TNBC and as a therapeutic target.
  • Methods: Genes that are involve in the glycolysis pathway of TNBC obtained by Genecard database. These genes were copied in string web server, the results exported by TSV format. The original nodes were determined by Cytoscape software. KEGG database was used to clarify pathways involved by the original nodes.
  • Results: Data obtained from the Genecards shown 338 genes along the glycolysis pathway of TNBC are important. AKT1, TP53, MAPK1, EGFR, CTNNB1, HIF1A, MTOR, PIK3CA, STAT3, MAPK8, NFKB1, PTEN, MAPK14, TNF, are genes with high degree among the 38 genes. Those have Regulation of eIF4e and p70 S6 Kinase, Stat3 Signaling Pathway, Human Cytomegalovirus, and Map Kinase Pathways, Role of ERBB2 in Signal Transduction and Oncology, EGF Signaling Pathway respectively.
  • Conclusion: The analysis genes showed that there are some common crucial genes including AKT1, TP53, MAPK1, EGFR, CTNNB1, HIF1A, MTOR, which are the key and controlling along this pathway. Therefore, these genes and pathway can be considered as an appropriate target for the control and treatment of TNBC.
  • Keywords: TNBC, Important genes, Glycolysis pathway, Genecards