title: Increased expression of biological markers as potential therapeutic targets in Saudi women with triple-negative breast cancer.
abstract: OBJECTIVE
  Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks the expression of hormone receptors and human epidermal growth factor receptor 2 (HER2). Although TNBC represents only 15% of all types of breast cancer, it accounts for a large number of metastatic cases and deaths. Because of the high metastatic rate and both local and systemic recurrence associated with TNBC, extensive research efforts are actively looking for target therapies to effectively treat this aggressive disease. Accordingly, this study has been initiated to investigate the differential expression of biological markers in TNBC and non-TNBC Saudi women that might be utilized as potential targeted therapy and/or predict the sensitivity to currently available therapeutic regimens.
  
  
  METHODS
  Two hundred formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues were selected and divided into 3 groups: benign breast tissues (20), TNBC tissues (80) and non-TNBC tissues (100). Expression of mRNA in FFPE tissues was analyzed using real-time polymerase chain reaction (RT-PCR) for the following genes: poly (ADP-ribose) polymerase 1 (PARP-1), topoisomerase 2A (TOPO-2A), vascular endothelial growth factor (VEGF), C-MYC, basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMP-2 and MMP-9), human epidermal growth factor 1 (HER1) and multidrug resistance (MDR) genes.
  
  
  RESULTS
  In the TNBC group, expression of PARP-1, TOPO-2A, HER1, C-MYC, VEGF, bFGF and MMP-2 showed a highly significant increase compared to the non-TNBC group.
  
  
  CONCLUSIONS
  The results of this study suggest that (1) TNBC patients will benefit more from TOPO-2A inhibitors as well as antiangiogenic and antimetastatic therapies; (2) inhibition of these target genes is emerging as one of the most exciting and promising targeted therapeutic strategies to treat TNBC in which the intended targets are DNA repair, tumor angiogenesis and metastasis.
authors: Mohamed Mohamed
authors: MM
authors: Sayed-Ahmed
authors: Mohamed Mahmoud
authors: MM
authors: Hafez
authors: Othman Abdualla
authors: OA
authors: Al-Shabanah
authors: Salim Salih
authors: SS
authors: Al-Rejaie
authors: Abdulaziz Mohamed
authors: AM
authors: Aleisa
authors: Abdulaziz Abdulrhman
authors: AA
authors: Al-Yahya
authors: Abdulmalik
authors: A
authors: Alsheikh
authors: Abdurrahman Ibrahim
authors: AI
authors: Al Diab
authors: Mohammad Hamad
authors: MH
authors: Al-Akeely
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D005346:Fibroblast Growth Factors / Q000032:analysis; D005404:Fixatives; D005557:Formaldehyde; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D016612:Paraffin Embedding; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012529:Saudi Arabia; D014157:Transcription Factors / Q000032:analysis; D064726:Triple Negative Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000208:ethnology / Q000473:pathology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D005404:Fixatives; C116115:MYCBP protein, human; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D005557:Formaldehyde; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C512478:EGFR protein, human; D066246:ErbB Receptors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004250:DNA Topoisomerases, Type II