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循环游离DNA作为转移性癌症患者分子监测工具的评估

Evaluation of circulating cell-free DNA as a molecular monitoring tool in patients with metastatic cancer.

作者信息

Hufnagl Clemens, Leisch Michael, Weiss Lukas, Melchardt Thomas, Moik Martin, Asslaber Daniela, Roland Geisberger, Steininger Philipp, Meissnitzer Thomas, Neureiter Daniel, Greil Richard, Egle Alexander

机构信息

Institute of Pathology, Paracelsus Medical University Salzburg, A-5020 Salzburg, Austria.

IIIrd Medical Department with Hematology and Medical Oncology, Oncologic Center, Paracelsus Medical University Salzburg, A-5020 Salzburg, Austria.

出版信息

Oncol Lett. 2020 Feb;19(2):1551-1558. doi: 10.3892/ol.2019.11192. Epub 2019 Dec 9.

DOI:10.3892/ol.2019.11192
PMID:31966080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6956108/
Abstract

The clinical decisions made when treating patients with metastatic cancer require knowledge of the current tumor extent and response to therapy. For the majority of solid tumors, a response assessment, which is based on imaging, is used to guide these decisions. However, measuring serum protein biomarkers (i.e. tumor markers) may be of additional use. Furthermore, tumor markers exhibit variable specificity and sensitivity and cannot therefore be solely relied upon when making decisions regarding cancer treatment. Therefore, there is a clinical requirement for the identification of specific, sensitive and quantitative biomarkers. In recent years, circulating cell-free DNA (cfDNA) and mutation-specific circulating cell-free tumor DNA (cftDNA) have been identified as novel potential biomarkers. In the current study, cfDNA and cftDNA were compared using imaging-based staging and current tumor markers in 15 patients with metastatic colorectal, pancreatic or breast cancer. These patients were treated at the Third Medical Department of Paracelsus Medical University Salzburg (Austria). The results of the current study demonstrated a statistically significant correlation between the concentration changes of cfDNA and cftDNA and response to treatment, which was assessed by imaging. A correlation was not indicated with current clinically used tumor markers, including carcinoembryonic antigen, carcinoma antigen 15-3 and carcinoma antigen 19-9. The present study also indicated a correlation between cfDNA and cftDNA and the tumor volume of metastatic lesions, which was not observed with the current clinically used tumor markers. In conclusion, cfDNA and cftDNA exhibit the potential to become novel biomarkers for the response assessment following cancer treatment, and may serve as a tool for the estimation of tumor volume. The current study further supports the increasingly important role of cfDNA and cftDNA as new monitoring tools for use during cancer therapy.

摘要

在治疗转移性癌症患者时做出的临床决策需要了解当前肿瘤的范围以及对治疗的反应。对于大多数实体瘤,基于影像学的反应评估用于指导这些决策。然而,检测血清蛋白生物标志物(即肿瘤标志物)可能会有额外的用途。此外,肿瘤标志物表现出不同的特异性和敏感性,因此在做出癌症治疗决策时不能仅仅依赖它们。因此,临床上需要鉴定特异性、敏感性和定量的生物标志物。近年来,循环游离DNA(cfDNA)和突变特异性循环游离肿瘤DNA(cftDNA)已被确定为新型潜在生物标志物。在本研究中,对15例转移性结直肠癌、胰腺癌或乳腺癌患者的cfDNA和cftDNA与基于影像学的分期及当前肿瘤标志物进行了比较。这些患者在奥地利萨尔茨堡帕拉塞尔苏斯医科大学第三医学部接受治疗。本研究结果表明,cfDNA和cftDNA的浓度变化与通过影像学评估的治疗反应之间存在统计学上的显著相关性。与目前临床使用的肿瘤标志物,包括癌胚抗原、癌抗原15-3和癌抗原19-9之间未显示相关性。本研究还表明cfDNA和cftDNA与转移灶的肿瘤体积之间存在相关性,而目前临床使用的肿瘤标志物未观察到这种相关性。总之,cfDNA和cftDNA有潜力成为癌症治疗后反应评估的新型生物标志物,并可作为估计肿瘤体积的工具。本研究进一步支持了cfDNA和cftDNA作为癌症治疗期间新的监测工具日益重要的作用。

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