NanoScience Technology Center and Department of Chemistry, University of Central Florida, 12424 Research Parkway, Orlando, FL 32826, USA.
J Transl Med. 2012 Mar 9;10:44. doi: 10.1186/1479-5876-10-44.
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.
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，预测患者因前列腺癌死亡风险的最相关预后因素是活检组织样本的 Gleason 评分。然而，病理分析具有主观性，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肿瘤侵袭性的分子生物标志物和诊断测试相当有限。
我们在这里首次报告了一种纳米粒子测试的开发，该测试不仅可以区分前列腺癌与正常和良性情况，而且还具有定量预测前列腺癌侵袭性的潜力。进行测试时，将前列腺组织裂解物样品掺入血清或人 IgG 溶液中，并将掺入的样品与柠檬酸保护的金纳米粒子溶液孵育。已知 IgG 吸附到柠檬酸保护的金纳米粒子上，在纳米粒子表面形成“蛋白质冠”。从这项研究中，我们发现某些肿瘤特异性分子可以与 IgG 相互作用，并改变 IgG 对金纳米粒子的吸附行为。这种变化反映在测定溶液中的纳米粒子大小上，并通过动态光散射技术检测到。通过单向方差分析对多变量分析进行分析，并使用学生 t 检验或非参数曼-惠特尼 U 检验进行成对分析。
从纳米粒子测试中观察到，测定溶液中平均纳米粒子大小与肿瘤状态和组织学诊断分级呈反比的定量相关性。与正常和良性组织相比，掺入前列腺肿瘤组织的 IgG 溶液显示出明显较小的纳米粒子尺寸。肿瘤分级越高，纳米粒子尺寸越小。该测试特别揭示了中级 2 级肿瘤之间的巨大差异，并表明需要对其进行不同的治疗。
新的纳米粒子测试的开发可能为前列腺癌的侵袭性提供定量测量。如果在更大的前列腺癌患者研究中得到验证，该测试可能成为与 Gleason 评分病理诊断相结合的新诊断工具，以更好地区分侵袭性癌症和惰性肿瘤。
