Role of circulating free DNA in evaluating clinical tumor burden and predicting survival in Chinese metastatic colorectal cancer patients.
Role of circulating free DNA in evaluating clinical tumor burden and predicting survival in Chinese metastatic colorectal cancer patients.
复制标题
循环游离DNA在评估中国转移性结直肠癌患者临床肿瘤负荷和预测生存中的作用
DOI：
10.1186/s12885-020-07516-7
复制
发表时间：
2020-10-16
期刊：
影响因子：
3.8
通讯作者：
Liu T
中科院分区：
文献类型：
--
作者：
Xu X;Yu Y;Shen M;Liu M;Wu S;Liang L;Huang F;Zhang C;Guo W;Liu T
本研究的目的是探讨循环游离DNA（cfDNA）在评估中国转移性结直肠癌（mCRC）患者临床肿瘤负荷和生存中的效用，并初步总结一些与突变状态相关的转移特征。采用涵盖 KRAS、NRAS、BRAF 和 PIK3CA 共 197 个热点突变的面板，通过下一代测序 (NGS) 技术评估 126 名 mCRC 患者血浆中的突变状态。使用扩增阻滞突变系统 (ARMS) 分析匹配组织样本中的基因组 DNA。收集血清中癌胚抗原（CEA）、碳水化合物抗原199（CA199）、碳水化合物抗原125（CA125）、神经元特异性烯醇化酶（NSE）和乳酸脱氢酶（LDH）等临床标志物以及CT或PET/CT上所有肿瘤直径的总和来指示临床肿瘤负荷。使用 Pearson 相关和线性回归模型分析 cfDNA 与临床肿瘤负荷之间的相关性。通过 Kaplan-Meier (K-M) 生存分析计算中位无进展生存期 (PFS) 和 1 年总生存率 (OS)。在126名入组患者中，血浆突变检测呈阳性的患者占45.2%（57/126）。分别有 37.3% (47/126)、1.6% (2/126)、3.2% (4/126) 和 13.5% (17/126) 的患者检测到 KRAS、NRAS、BRAF 和 PIK3CA 突变。血浆和匹配组织之间突变状态的总体一致性为78.6%（99/126）。十六名患者的血浆中存在组织中未检测到的突变，其中包括一些罕见的热点突变。 cfDNA浓度与临床标志物水平显着相关，特别是CEA（P < 0.0001，Pearson r = 0.81）、LDH（P < 0.0001，Pearson r = 0.84）和肿瘤直径总和（P < 0.0001，Pearson） r = 0.80）。与低cfDNA浓度的患者相比，高cfDNA浓度（>17.91ng/ml）的患者中位无进展生存期较短（6.6个月与11.7个月，P<0.0001），1年总生存率较低（56%对94%，P<0.0001） (≤17.91 ng/ml)。所有患者中最常见的转移部位是肝脏（77.8%），其次是淋巴结（62.7%）、肺（40.5%）、腹膜（14.3%）和骨（10.3%）。不同突变状态之间的转移没有显着差异。与分析组织中的突变相比，分析血浆中的突变可以提供更全面的突变景观概述。 cfDNA浓度可以作为肿瘤负荷的定量生物标志物，并可以预测中国转移性结直肠癌患者的生存率。
The aim of this study was to explore the utility of circulating free DNA (cfDNA) in the evaluation of clinical tumor burden and survival in Chinese patients with metastatic colorectal cancer (mCRC) and to preliminarily summarize some metastatic characteristics associated with mutational status. A panel covering a total of 197 hotspot mutations of KRAS, NRAS, BRAF and PIK3CA was used to evaluate the mutational status in plasma by next-generation sequencing (NGS) technology in 126 patients with mCRC. An amplification-refractory mutation system (ARMS) was used to analyze genomic DNA from matched tissue samples. Clinical markers including carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) in serum and the sum of all tumor diameters on CT or PET/CT were collected to indicate clinical tumor burden. The correlations between cfDNA and clinical tumor burden were analyzed using Pearson correlation and linear regression models. The median progression-free survival (PFS) and 1-year overall survival (OS) rates were calculated by Kaplan-Meier (K-M) survival analysis. Of the 126 enrolled patients, patients who were tested positive for mutations in plasma accounted for 45.2% (57/126). Mutations in KRAS, NRAS, BRAF and PIK3CA were detected in 37.3% (47/126), 1.6% (2/126), 3.2% (4/126) and 13.5% (17/126) of patients, respectively. The overall concordance rate of mutational status between plasma and matched tissues was 78.6% (99/126). Sixteen patients had mutations in plasma that were not detected in tissue, including some rare hotspot mutations. The cfDNA concentration was significantly correlated with the levels of clinical markers, especially CEA (P < 0.0001, Pearson r = 0.81), LDH (P < 0.0001, Pearson r = 0.84) and the sum of tumor diameters (P < 0.0001, Pearson r = 0.80). Patients with a high cfDNA concentration (> 17.91 ng/ml) had shorter median progression-free survival (6.6 versus 11.7 months, P < 0.0001) and lower 1-year overall survival rate (56% versus 94%, P < 0.0001) than those with a low cfDNA concentration (≤17.91 ng/ml). The most common metastatic site was the liver (77.8%), followed by the lymph nodes (62.7%), lung (40.5%), peritoneum (14.3%) and bone (10.3%), in all patients. There was no significant difference in metastasis between different mutational statuses. Analyzing mutations in plasma could provide a more comprehensive overview of the mutational landscape than analyzing mutations in tissue. The cfDNA concentration could be a quantitative biomarker of tumor burden and could predict survival in Chinese patients with mCRC.
登录
查看更多内容
DOI：
10.1186/s13046-018-0723-5
发表时间：
2018-03-12
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Thomsen CB;Hansen TF;Andersen RF;Lindebjerg J;Jensen LH;Jakobsen A
通讯作者：
Jakobsen A
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1093/annonc/mdx112
发表时间：
2017-06-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Grasselli J;Elez E;Caratù G;Matito J;Santos C;Macarulla T;Vidal J;Garcia M;Viéitez JM;Paéz D;Falcó E;Lopez Lopez C;Aranda E;Jones F;Sikri V;Nuciforo P;Fasani R;Tabernero J;Montagut C;Azuara D;Dienstmann R;Salazar R;Vivancos A
通讯作者：
Vivancos A
影响因子：
11.5
作者：
Baldus, Stephan E.;Schaefer, Karl-L.;Gabbert, Helmut E.
通讯作者：
Gabbert, Helmut E.
影响因子：
50.5
作者：
Bokemeyer, C.;Bondarenko, I.;Koralewski, P.
通讯作者：
Koralewski, P.