Enhanced detection of cell-free DNA (cfDNA) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer.

Enhanced detection of cell-free DNA (cfDNA) enables its use as a reliable biomarker for diagnosis and prognosis of gastric cancer.
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增强了无细胞DNA(CFDNA)的检测,它可以用作可靠的生物标志物来诊断和预后的胃癌。

DOI:
10.1371/journal.pone.0242145
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发表时间:
2020
期刊:
影响因子:
3.7
通讯作者:
Hyun SH
Hyun SH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bu J;Lee TH;Jeong WJ;Poellmann MJ;Mudd K;Eun HS;Liu EW;Hong S;Hyun SH

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尽管循环游离DNA(cfDNA)是用于各种肿瘤的诊断和预后的有希望的生物标志物,但cfDNA与胃癌的临床相关性尚未完全了解。为了解决这个问题,我们通过整合聚多巴胺(PDA)和二氧化硅开发了高度灵敏的cfDNA捕获系统。PDA-二氧化硅杂合物将不同的分子相互作用并入单个系统,与常规的基于二氧化硅的方法相比,将cfDNA捕获增强了1.34倍(p = 0.001),这使用细胞培养物上清液证实。一项使用人血浆样本的临床研究表明,新系统的诊断准确性优于市售cfDNA试剂盒以及其他血清抗原检测,具有上级性。在癌症患者中,血浆cfDNA水平表现出与肿瘤大小的良好相关性。cfDNA也是远处转移的预测因子,因为转移性癌症患者的中值cfDNA水平比没有转移的患者高约60倍(p = 0.008)。此外,发现组织活检和cfDNA基因组分析之间的高度一致性,因为cfDNA中的HER 2表达显示用于检测具有HER 2阳性肿瘤的患者的ROC曲线下面积(AUC)为0.976(p <0.001)。新系统还揭示了cfDNA的高预后能力,因为cfDNA的浓度与生存结果高度相关。我们的新技术证明了实现cfDNA的有效检测的潜力,cfDNA可以作为胃肿瘤的可靠生物标志物。
Although circulating cell-free DNA (cfDNA) is a promising biomarker for the diagnosis and prognosis of various tumors, clinical correlation of cfDNA with gastric cancer has not been fully understood. To address this, we developed a highly sensitive cfDNA capture system by integrating polydopamine (PDA) and silica. PDA-silica hybrids incorporated different molecular interactions to a single system, enhancing cfDNA capture by 1.34-fold compared to the conventional silica-based approach (p = 0.001), which was confirmed using cell culture supernatants. A clinical study using human plasma samples revealed that the diagnostic accuracy of the new system to be superior than the commercially available cfDNA kit, as well as other serum antigen tests. Among the cancer patients, plasma cfDNA levels exhibited a good correlation with the size of a tumor. cfDNA was also predicative of distant metastasis, as the median cfDNA levels of metastatic cancer patients were ~60-fold higher than those without metastasis (p = 0.008). Furthermore, high concordance between tissue biopsy and cfDNA genomic analysis was found, as HER2 expression in cfDNA demonstrated an area under ROC curve (AUC) of 0.976 (p <0.001) for detecting patients with HER2-positive tumors. The new system also revealed high prognostic capability of cfDNA, as the concentration of cfDNA was highly associated with the survival outcomes. Our novel technology demonstrates the potential to achieve efficient detection of cfDNA that may serve as a reliable biomarker for gastric tumor.
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在不同的缓冲液,pH和离子强度条件下,多最多DNA吸附到二氧化硅表面。
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