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Therapeutic Potential of Plk1, Kif4a, Cdca5, Ube2c, Cdt1, Ska3, Aurkb, and Pttg1 Genes in Triple-Negative Breast Cancer: Correlating Their Expression With Sensitivity to Gsk 461364 and Ikk 16 Drugs Publisher



Bashari N1, 4 ; Naghizadeh M2, 4 ; Chegini MK3, 4 ; Sadeghi ES4 ; Zamani A4, 5 ; Mahdevar M4, 6
Authors
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Authors Affiliations
  1. 1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
  2. 2. Dalian Medical University, Liaoning, China
  3. 3. Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  4. 4. Genius Gene, Genetics and Biotechnology Company, Isfahan, Iran
  5. 5. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
  6. 6. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Biochemical Genetics Published:2024


Abstract

The treatment of triple-negative breast cancer (TNBC) has been associated with challenges due to the lack of expression of ER, PR, and HER2 receptors in tumor cells. This study aimed to identify genes with potential therapeutic targets in TNBC. Data from the cancer genome atlas regarding breast cancer (BC) were downloaded. After initial preprocessing, cancer samples were categorized into four groups: TNBC, HER2-positive, luminal A, and luminal B. Gene expression differences between these groups were calculated, focusing on genes that showed differential expression in TNBC. A protein–protein interaction network was conducted to identify hub genes among the candidate genes related to TNBC. The protein expression of candidate genes was assessed using immunohistochemistry data from the human protein atlas. Drug resistance and sensitivity associated with hub genes were identified using data from PharmacoDB. TNBC samples and the RT-qPCR method were used to confirm the results. Our findings revealed that eight genes, namely PLK1, KIF4A, CDCA5, UBE2C, CDT1, SKA3, AURKB, and PTTG1, had significant upregulation at the RNA level in TNBC subgroup compared to other subgroups and could be considered hub genes in TNBC. Compared to other subgroups, their expression level in TNBC samples had high sensitivity and specificity. RT-qPCR results also demonstrated a significant increase in levels of SKA3 and PTTG1 in the TNBC compared to healthy tissue and other subgroups. The protein expression of these genes was notably high in some BC samples. PharmacoDB data showed that some candidate genes were closely linked to drug sensitivity of GSK 461364 and IKK 16. The results of this study showed a significant increase in the expression level of PLK1, KIF4A, CDCA5, UBE2C, CDT1, SKA3, AURKB, and PTTG1 in TNBC compared to other BC subgroups. These genes show considerable promise as therapeutic targets for the TNBC subgroup. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
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