Increased level and fragmentation of plasma circulating cell-free DNA are diagnostic and prognostic markers for renal cell carcinoma.
Increased level and fragmentation of plasma circulating cell-free DNA are diagnostic and prognostic markers for renal cell carcinoma.
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DOI：
10.18632/oncotarget.24943
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发表时间：
2018-04-17
期刊：
影响因子：
--
通讯作者：
Nonomura, Norio
中科院分区：
文献类型：
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作者：
Yamamoto, Yoshiyuki;Uemura, Motohide;Nonomura, Norio
背景：肾细胞癌(RCC)的可靠生物标志物尚未找到。循环中的无细胞DNA(CfDNA)是一种新的诊断和预测多种癌症的资源。本研究旨在寻找新的肾癌血液标志物。材料和方法：从92例肾癌患者和41例健康对照中提取血浆cfDNA。以ACTB为靶基因，实时定量聚合酶链式反应检测cfDNA水平，微流控平台测定cfDNA片段大小。结果：肾癌患者cfDNA中位数水平显著高于正常对照组(3803vs2242拷贝/ml，p<；0.001)。肾细胞癌患者的cfDNA片段大小中位数较健康对照组短(170vs171bp，p=0.052)。评价cfDNA水平对肾癌的诊断价值，ROC曲线分析的敏感性为63.0%，特异性为78.1%。多因素分析显示，年龄、性别和cfDNA水平与肾癌的发生显著相关(p<；0.001，p=0.013，p<；0.001)。此外，较短的cfDNA片段大小与无进展生存期呈负相关(p=0.006)。结论：我们的研究证实了血浆cfDNA作为肾癌生物标志物的诊断和预后潜力。
BACKGROUND: Reliable biomarkers for renal cell carcinoma (RCC) have yet to be found. Circulating cell-free DNA (cfDNA) is an emerging resource for the diagnosis and prognosis of various cancers. This study aims to identify novel blood biomarkers for RCC.MATERIALS AND METHODS: Plasma cfDNA was extracted from RCC patients (n = 92) and healthy controls (n = 41). Levels of cfDNA were determined using quantitative real-time PCR of ACTB as the target gene, and cfDNA fragment size was measured using a microfluidics-based platform. Diagnostic potential was assessed using receiver operating characteristic (ROC) and logistic regression analysis, and prognostic potential was evaluated using log-rank test.RESULTS: Median levels of cfDNA from RCC patients were significantly higher than those from healthy controls (3803 vs 2242 copies/ml, p < 0.001). Median fragment sizes of cfDNA in RCC patients were shorter than those in healthy controls (170 vs 171 bp, p = 0.052). To evaluate level of cfDNA as a diagnostic tool for RCC, ROC curve analysis revealed a sensitivity of 63.0% and a specificity of 78.1%. Multivariate analysis indicated that age, gender and the level of cfDNA were significantly associated with the presence of RCC (p < 0.001, p = 0.013, p < 0.001, respectively). Additionally, shorter cfDNA fragment size was negatively associated with progression-free survival (p = 0.006).CONCLUSIONS: Our study demonstrates the diagnostic and prognostic potential of plasma cfDNA as a biomarker for RCC.