接受新辅助化疗的乳腺癌患者血浆 ccfDNA、mtDNA 变化、CTC 与上皮间质转化的相关性。
Correlation between plasma ccfDNA, mtDNA changes, CTCs, and epithelial-mesenchymal transition in breast cancer patients undergoing NACT.
机构信息
Department of Medical Biology and Genetics, Health Sciences Institute, Marmara University, İstanbul, Turkiye.
Department of Medical Biology, School of Medicine, Marmara University, İstanbul, Turkiye.
出版信息
Turk J Med Sci. 2024 Mar 11;54(4):652-665. doi: 10.55730/1300-0144.5834. eCollection 2024.
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.
背景/目的：乳腺癌是女性最常见的癌症，因此需要寻找非侵入性的血液生物标志物来辅助治疗方案的选择。先前的研究已经证明乳腺癌患者的血浆循环无细胞 DNA（ccfDNA）水平升高。ccfDNA 和线粒体 DNA（mtDNA）都是释放到血液中的片段。在这项研究中，我们研究了 ccfDNA 和 mtDNA 作为治疗反应指标的有效性，并探索了它们作为监测生物标志物的潜力。此外，我们将这些标志物与循环肿瘤细胞（CTC）数据进行了比较，并评估了它们与上皮间质转化（EMT）的关系。
材料和方法
本研究纳入了 36 名女性乳腺癌患者和 21 名健康女性。通过定量聚合酶链反应（qPCR）对血浆样本进行检测，以测量 ND1、ND4、ALU115、ALU247 和 GAPDH 的水平，并通过计算 ALU247/ALU115 和 ND4/ND1 的比值来确定 DNA 完整性。
结果
治疗后，患者的 ccfDNA 水平显著降低，mtDNA 拷贝数（mtDNAcn）显著增加。然而，ccfDNA 和 mtDNA 完整性没有显著变化。在比较所有组时，与对照组相比，患者的 ALU115 和 ALU247 水平更高。此外，患者的 ccfDNA 完整性明显低于对照组。
结论
本研究首次全面研究了血浆 ccfDNA 水平、mtDNAcn 和完整性。此外，这也是首次探索这些标志物与 CTCs、癌症干细胞标志物、治疗反应和转移状态之间关系的研究。我们的研究结果表明，血浆 ccfDNA 和 mtDNA 可能作为评估化疗反应的潜在生物标志物，可单独或与其他标志物联合用于监测乳腺癌患者的治疗效果。
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