Correlation between plasma ccfDNA, mtDNA changes, CTCs, and epithelial-mesenchymal transition in breast cancer patients undergoing NACT


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Çelik B., PEKER EYÜBOĞLU İ., Koca S., Ümit Uğurlu M., Alan Ö., GÜLLÜ AMURAN G., ...Daha Fazla

Turkish Journal of Medical Sciences, cilt.54, sa.4, ss.652-665, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 54 Sayı: 4
  • Basım Tarihi: 2024
  • Doi Numarası: 10.55730/1300-0144.5834
  • Dergi Adı: Turkish Journal of Medical Sciences
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, MEDLINE, Veterinary Science Database, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.652-665
  • Anahtar Kelimeler: Breast cancer, ccfDNA, EMT, mtDNA, neoadjuvant therapy
  • Marmara Üniversitesi Adresli: Evet

Özet

Background/aim: Breast cancer is the most prevalent cancer in women, emphasizing need for noninvasive blood biomarkers to aid in treatment selection. Previous studies have demonstrated elevated levels of plasma circulating cell-free DNA (ccfDNA) in breast cancer patients. Both ccfDNA and mitochondrial DNA (mtDNA) are fragments released into the bloodstream. In this study, we investigated effectiveness of ccfDNA and mtDNA as indicators of treatment response and explored their potential as monitoring biomarkers. Additionally, we compared these markers with circulating tumor cell (CTC) data and assessed their relationship with epithelial-mesenchymal transition (EMT). Materials and methods: Thirty-six female breast cancer patients and 21 healthy females were included in the study. Quantitative polymerase chain reaction (qPCR) was performed on plasma samples to measure levels of ND1, ND4, ALU115, ALU247, and GAPDH, and DNA integrity was determined by calculating ratios of ALU247/ALU115 and ND4/ND1. Results: After treatment, patients had a significant decrease in ccfDNA levels and a significant increase in mtDNA copy number (mtDNAcn). However, there was no significant change in ccfDNA and mtDNA integrity. When comparing all groups, patients exhibited higher levels of ALU115 and ALU247 compared to controls. Moreover, patients demonstrated significantly lower ccfDNA integrity than controls. Conclusion: This study represents the first comprehensive investigation of plasma ccfDNA levels, mtDNAcn, and integrities collectively. Furthermore, it is the first study to explore the relationship between these markers and CTCs, cancer stem cell markers, treatment response, and metastatic status. Our findings suggest that plasma ccfDNA and mtDNA may serve as potential biomarkers for assessing chemotherapy response and can be employed alone or in combination with other biomarkers to monitor treatment efficacy in breast cancer patients.