Quantification of circulating cell-free DNA in the plasma of cancer patients during radiation therapy
Quantification of circulating cell-free DNA in the plasma of cancer patients during radiation therapy
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DOI：
10.1111/j.1349-7006.2008.01021.x
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发表时间：
2009-02-01
期刊：
影响因子：
5.7
通讯作者：
Inoue, Tomio
中科院分区：
文献类型：
--
作者：
Cheng, Chao;Omura-Minamisawa, Motoko;Inoue, Tomio
癌症患者的无细胞血浆DNA升高，并在有效治疗后降低。因此，这些核酸具有作为新的肿瘤标志物的潜力。在我们目前的研究中，我们调查了癌症患者的血浆DNA浓度在放射治疗过程中是否发生了变化。为了首先确定无细胞血浆DNA的来源，分析来自携带移植的人肿瘤的小鼠的血浆样品的人特异性和小鼠特异性无细胞DNA。仅在荷瘤小鼠的血浆中可检测到人类特异性DNA。然而，小鼠特异性血浆DNA在荷瘤小鼠中显著高于正常小鼠，表明无细胞血浆DNA来源于肿瘤细胞和正常细胞。我们通过定量聚合酶链反应测定了15例接受放射治疗的癌症患者的血浆总游离DNA水平，并将这些值与健康对照组进行了比较。癌症患者的治疗前血浆DNA浓度高于健康对照组。其中11名患者在放射治疗的第一周或第二周表现出高达8倍的血浆游离DNA浓度一过性增加，随后在治疗结束时浓度下降。在另外两名癌症患者中，游离血浆DNA浓度仅在治疗过程中下降。因此，癌症患者的总游离血浆DNA水平显示出与放射治疗进展相关的动态变化。将需要额外的前瞻性研究来阐明放射治疗期间游离血浆DNA动态变化的潜在临床效用和生物学意义。（Cancer Sci 2009; 100：303-309）。
Cell-free plasma DNA is elevated in cancer patients and decreases in response to effective treatments. Consequently, these nucleic acids have potential as new tumor markers. In our current study, we investigated whether the plasma DNA concentrations in patients with cancer are altered during the course of radiation therapy. To first determine the origin of cell-free plasma DNA, plasma samples from mice bearing transplanted human tumors were analyzed for human-specific and mouse-specific cell-free DNA. Human-specific DNA was detectable only in plasma from tumor-bearing mice. However, mouse-specific plasma DNA was significantly higher in tumor-bearing mice than in normal mice, suggesting that cell-free plasma DNA originated from both tumor and normal cells. We measured the total cell-free plasma DNA levels by quantitative polymerase chain reaction in 15 cancer patients undergoing radiation therapy and compared these values with healthy control subjects. The cancer patients showed higher pretreatment plasma DNA concentrations than the healthy controls. Eleven of these patients showed a transient increase of up to eightfold in their cell-free plasma DNA concentrations during the first or second week of radiation therapy, followed by decreasing concentrations toward the end of treatment. In two other cancer patients, the cell-free plasma DNA concentrations only decreased over the course of the treatment. The total cell-free plasma DNA levels in cancer patients thus show dynamic changes associated with the progression of radiation therapy. Additional prospective studies will be required to elucidate the potential clinical utility and biological implications of dynamic changes in cell-free plasma DNA during radiation therapy. (Cancer Sci 2009; 100: 303-309).