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

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-03-11 eCollection Date: 2024-01-01 DOI:10.55730/1300-0144.5834

Betül Çelik, İrem Peker Eyüboğlu, Sinan Koca, M Ümit Uğurlu, Özkan Alan, Gökçe Güllü Amuran, Tuğba Akin Telli, Fulden Yumuk, Mustafa Akkiprik

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引用次数: 0

Abstract

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.

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接受 NACT 治疗的乳腺癌患者血浆 ccfDNA、mtDNA 变化、CTCs 和上皮-间质转化之间的相关性。

背景/目的：乳腺癌是女性发病率最高的癌症，因此需要无创血液生物标志物来帮助选择治疗方法。以往的研究表明，乳腺癌患者血浆循环游离细胞 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记物的潜力。此外，我们还将这些标记物与循环肿瘤细胞（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：研究对象包括 36 名女性乳腺癌患者和 21 名健康女性。对血浆样本进行定量聚合酶链反应（qPCR），以测量 ND1、ND4、ALU115、ALU247 和 GAPDH 的水平，并通过计算 ALU247/ALU115 和 ND4/ND1 的比率来确定 DNA 的完整性：治疗后，患者的ccfDNA水平明显下降，mtDNA拷贝数（mtDNAcn）明显增加。但是，ccfDNA和mtDNA的完整性没有明显变化。在比较所有组别时，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：本研究首次对血浆ccfDNA水平、mtDNAcn和整合度进行了全面调查。此外，这是首次探讨这些标记物与 CTCs、癌症干细胞标记物、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可作为评估化疗反应的潜在生物标志物，可单独使用或与其他生物标志物结合使用，以监测乳腺癌患者的治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.