检测循环肿瘤DNA追踪黑色素瘤进展

检验之星

2016年1月19日讯 /生物谷BIOON/ --最近一项新研究报道称一种血液检测方法能够发现血液中死亡癌细胞的DNA片段，利用这种方法跟踪预测转移性黑色素瘤的进展和潜在扩散能力要比目前使用的标准检测方法更好。这项研究由纽约大学的研究人员领导完成，发表在国际学术期刊Molecular Oncology上。

目前临床使用的标准检测方法需要检测血液中乳酸脱氢酶的表达水平。这种酶在侵袭性肿瘤生长过程中会大量增加，但同时其他一些疾病以及生物学过程的发生也会增加该酶的表达。而检测肿瘤细胞死亡之后进入血液的循环肿瘤DNA可能是检测侵袭性肿瘤的一种很好的替代方法。

这项研究中包含了31名不宜进行手术治疗的转移性黑色素瘤病人，这些病人均包含BRAF基因突变以及NRAS基因突变两者之中的其中一种，许多研究已经证明这两个基因上发生的突变与黑色素瘤发生密切相关。这些病人在治疗之后都进行了循环肿瘤DNA以及LDH两种血液检测，大部分人在治疗之前也进行了这两种检测，同时以没有患黑色素瘤的30名正常人的血液检测结果作为对照。

研究人员发现80%将要接受治疗的转移性黑色素瘤病人（15名病人中的12人）体内血液中循环肿瘤DNA的水平升高，与之相比，在接受治疗之前仅有30%（23名病人中的7人）的病人出现血液中乳酸脱氢酶的水平升高。研究结果还表明在检测癌症复发方面，血液中循环肿瘤DNA也要比乳酸脱氢酶更加灵敏，这一结果也得到了X光片和CT扫描结果证实。

因此，这项研究表明检测血液中的循环肿瘤DNA水平可能是追踪预测黑色素瘤进展以及扩散情况的一种更好的方法。（生物谷Bioon.com）

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doi:10.1016/j.molonc.2015.09.005

Sensitivity of plasma BRAFmutant and NRASmutant cell-free DNA assays to detect metastatic melanoma in patients with low RECIST scores and non-RECIST disease progression

Gregory A. Changa, c, Jyothirmayee S. Tadepallia, c, Yongzhao Shaoc, d, Yilong Zhangc, d, Sarah Weissb, c, Eric Robinsona, c, Cindy Spittlee, Manohar Furtadof, Dawne N. Sheltonf, George Karlin-Neumannf, Anna Pavlickb, c, Iman Osmana, c, David Polsky

Melanoma lacks a clinically useful blood-based biomarker of disease activity to help guide patient management. To determine whether measurements of circulating, cell-free, tumor-associated BRAFmutant and NRASmutant DNA (ctDNA) have a higher sensitivity than LDH to detect metastatic disease prior to treatment initiation and upon disease progression we studied patients with unresectable stage IIIC/IV metastatic melanoma receiving treatment with BRAF inhibitor therapy or immune checkpoint blockade and at least 3 plasma samples obtained during their treatment course. Levels of BRAFmutant and NRASmutant ctDNA were determined using droplet digital PCR (ddPCR) assays. Among patients with samples available prior to treatment initiation ctDNA and LDH levels were elevated in 12/15 (80%) and 6/20 (30%) (p = 0.006) patients respectively. In patients with RECIST scores <5 cm prior to treatment initiation, ctDNA levels were elevated in 5/7 (71%) patients compared to LDH which was elevated in 1/13 (8%) patients (p = 0.007). Among all disease progression events the modified bootstrapped sensitivities for ctDNA and LDH were 82% and 40% respectively, with a median difference in sensitivity of 42% (95% confidence interval, 27%–58%; P < 0.001). In addition, ctDNA levels were elevated in 13/16 (81%) instances of non-RECIST disease progression, including 10/12 (83%) instances of new brain metastases. In comparison LDH was elevated 8/16 (50%) instances of non-RECIST disease progression, including 6/12 (50%) instances of new brain metastases. Overall, ctDNA had a higher sensitivity than LDH to detect disease progression, including non-RECIST progression events. ctDNA has the potential to be a useful biomarker for monitoring melanoma disease activity.

来源：生物谷