Extracellular mRNA detected by molecular beacons in tethered lipoplex nanoparticles for diagnosis of human hepatocellular carcinoma.
Extracellular mRNA detected by molecular beacons in tethered lipoplex nanoparticles for diagnosis of human hepatocellular carcinoma.
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DOI：
10.1371/journal.pone.0198552
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Lee LJ
中科院分区：
文献类型：
--
作者：
Wang X;Kwak KJ;Yang Z;Zhang A;Zhang X;Sullivan R;Lin D;Lee RL;Castro C;Ghoshal K;Schmidt C;Lee LJ
肝细胞癌（HCC）仍然是癌症相关死亡的主要原因之一。尽管超声检查 (US)、计算机断层扫描 (CT) 和/或高成本磁共振成像 (MRI) 已被证明可以改善肝癌的早期检测并降低高危人群的死亡率，但此类基于成像的方法受到高假阳性率的限制，导致患者不必要的焦虑和侵入性操作。补充血液生物标志物可以提高早期检测的准确性。尽管血液中的甲胎蛋白（AFP）广泛用于HCC筛查和诊断，但晚期HCC和早期HCC的假阴性率分别高达30%和40%。我们使用设计的分子信标和新型系留脂质复合物纳米颗粒 (TLN) 生物芯片检测了患者血浆细胞外囊泡 (EV) 中的 AFP 信使 RNA (mRNA)。与另一种众所周知的 HCC 标记物磷脂酰肌醇蛋白聚糖 3 (GPC-3) mRNA 一起，我们观察到基于 AFP 蛋白的 HCC 检测性能大大提高。比较正常供体 (N = 38) 和 HCC 患者 (N = 40)，我们使用 EV AFP 和 GPC-3 mRNA 的 TLN 生物芯片提供的 AUC（ROC 曲线下面积）为 0.995，优于单一标记物。这种 2-mRNA 组合还提供了完美的阳性预测值 (PPV = 1)，阴性预测值 (NPV) 为 0.95 和 20% 的患病率，而单独的血液 AFP 蛋白或血浆 EV GPC3 mRNA 在相同条件下只能分别提供 0.61 和 0.79 的 PPV。因此，这种简便的新方法可以补充当前肝癌筛查、治疗监测和治疗后监测中风险分层的模型。然而，需要进行大规模验证以确认其临床潜力。
Hepatocellular carcinoma (HCC) remains one of the major causes of cancer related deaths. Although ultrasonography (US), computed tomography (CT) and/or high-cost magnetic resonance imaging (MRI) have been shown to improve early detection of liver cancer and mortality rates in high-risk individuals, such imaging based methods are limited by high rates of false positivity leading to unnecessary patient anxiety and invasive procedures. Complementary blood biomarkers could increase the accuracy of early detection. Although Alpha-fetoprotein (AFP) in blood is widely used in HCC screening and diagnosis, the false-negative rate as high as 30% and 40% is found in advanced HCC and early stage HCC respectively. We detected AFP messenger RNA (mRNA) in extracellular vesicles (EVs) in patient plasma using designed molecular beacons and a novel tethered lipoplex nanoparticle (TLN) biochip. Together with glypican-3 (GPC-3) mRNA, another well-known HCC marker, we observed much improved performance of AFP protein-based HCC detection. Comparing normal donors (N = 38) and HCC patients (N = 40), our TLN biochip using EV AFP and GPC-3 mRNAs provided an AUC (area under the ROC curve) of 0.995, better than that of a single marker. This 2-mRNA combination also provided a perfect positive predictive value (PPV = 1) at a negative predictive value (NPV) of 0.95 and 20% prevalence, while the blood AFP protein or plasma EV GPC3 mRNA alone could only provide a PPV of 0.61 and 0.79 respectively at the same conditions. Thus, this facile new method may complement current models for risk stratification in liver cancer screening, therapeutic monitoring, and after-treatment surveillance. However, large scale validation will need to be conducted to confirm its clinical potential.
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影响因子：
2.9
作者：
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通讯作者：
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作者：
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影响因子：
3.7
作者：
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