Developing a nanoparticle test for prostate cancer scoring.
Developing a nanoparticle test for prostate cancer scoring.
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DOI：
10.1186/1479-5876-10-44
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发表时间：
2012-03-09
影响因子：
7.4
通讯作者：
Rivera-Ramirez I
中科院分区：
文献类型：
--
作者：
Huo Q;Litherland SA;Sullivan S;Hallquist H;Decker DA;Rivera-Ramirez I
前列腺癌的过度诊断和治疗一直是前列腺癌护理和管理中的一个主要问题。目前，预测患者前列腺癌死亡风险的最相关的预后因素是活检组织样本的Gleason评分。然而，病理分析是主观的，Gleason评分只是对癌症恶性程度的定性估计。能够准确预测前列腺癌侵袭性的分子生物标志物和诊断试验相当有限。我们在这里首次报告了一种纳米颗粒测试的发展，该测试不仅可以区分前列腺癌与正常和良性疾病，而且有可能定量预测前列腺癌的侵袭性。为了进行测试，将前列腺组织裂解液样本添加到血清或人类免疫球蛋白溶液中，并将添加的样本与柠檬酸保护的金纳米颗粒溶液孵育。已知的是，免疫球蛋白能吸附到柠檬酸保护的金纳米颗粒上，在纳米颗粒表面形成“蛋白质日冕”。通过这项研究，我们发现某些肿瘤特异性分子可以与免疫球蛋白相互作用，并改变免疫球蛋白对金纳米颗粒的吸附行为。这种变化反映在分析溶液的纳米颗粒大小上，并通过动态光散射技术进行检测。采用单因素方差分析进行多变量分析，采用学生t检验或非参数Mann-Whitney U检验进行配对分析。从纳米颗粒测试中观察到分析溶液的平均纳米颗粒大小与肿瘤状态和组织学诊断分级之间存在反向的定量相关性。与加入正常组织和良性组织的溶液相比，加入前列腺癌组织的免疫球蛋白溶液显示出明显更小的纳米颗粒尺寸。肿瘤分级越高，纳米颗粒越小。这项测试特别揭示了中级2级肿瘤之间的巨大差异，并建议有必要对它们进行不同的治疗。一种新的纳米颗粒测试的发展可能提供前列腺癌侵袭性的定量测量。如果在对前列腺癌患者的更大规模研究中得到验证，这项测试可能成为一种新的诊断工具，与格里森评分病理诊断相结合，更好地区分侵袭性癌症和惰性肿瘤。
Over-diagnosis and treatment of prostate cancer has been a major problem in prostate cancer care and management. Currently the most relevant prognostic factor to predict a patient's risk of death due to prostate cancer is the Gleason score of the biopsied tissue samples. However, pathological analysis is subjective, and the Gleason score is only a qualitative estimate of the cancer malignancy. Molecular biomarkers and diagnostic tests that can accurately predict prostate tumor aggressiveness are rather limited. We report here for the first time the development of a nanoparticle test that not only can distinguish prostate cancer from normal and benign conditions, but also has the potential to predict the aggressiveness of prostate cancer quantitatively. To conduct the test, a prostate tissue lysate sample is spiked into a blood serum or human IgG solution and the spiked sample is incubated with a citrate-protected gold nanoparticle solution. IgG is known to adsorb to citrate-protected gold nanoparticles to form a "protein corona" on the nanoparticle surface. From this study, we discovered that certain tumor-specific molecules can interact with IgG and change the adsorption behavior of IgG to the gold nanoparticles. This change is reflected in the nanoparticle size of the assay solution and detected by a dynamic light scattering technique. Assay data were analyzed by one-way ANOVA for multiple variant analysis, and using the Student t-test or nonparametric Mann-Whitney U-tests for pairwise analyses. An inverse, quantitative correlation of the average nanoparticle size of the assay solution with tumor status and histological diagnostic grading was observed from the nanoparticle test. IgG solutions spiked with prostate tumor tissue exhibit significantly smaller nanoparticle size than the solutions spiked with normal and benign tissues. The higher grade the tumor is, the smaller the nanoparticle size is. The test particularly revealed large differences among the intermediate Grade 2 tumors, and suggested the need to treat them differently. Development of a new nanoparticle test may provide a quantitative measure of the prostate cancer aggressiveness. If validated in a larger study of patients with prostate cancer, this test could become a new diagnostic tool in conjunction with Gleason Score pathology diagnostics to better distinguish aggressive cancer from indolent tumor.
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影响因子：
64.8
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