J Transl Med：恶性前列腺癌新诊断工具

六分之一的男性在他的一生会被诊断患有前列腺癌，前列腺癌是美国男性的第二大死因。

这是一个严重的问题，当前的诊断测试不尽如人意。近日，中央佛罗里达大学纳米科学技术中心的研究小组已经开发出一中更准确的测试技术，不仅能确定病人是否有前列腺癌，而且能测得所患前列癌的恶性程度如何。

该项目的首席研究员说副教授Qun Treen：我们的纳米粒子不仅能发现一个前列腺癌特异性的化学反应，他们也可以告诉我们癌细胞的恶性程度如何，它可以给医生提供更详细的信息来更好地治疗病人。当前的测试技术不能告诉我们癌症的恶性程度如何，这往往导致临床医生直接进行腺体切除手术，而不考虑其他治疗手段。

相关研究论文发表在Journal of Translational Medicine杂志上。研究人员表示该技术方法相当简单。

研究人员用黄金纳米粒子检测前列腺肿瘤和人类免疫球蛋白（IgG）之间的特定的化学反应。 IgG是血液中循环一个丰富的蛋白质。研究表明，IgG会与黄金纳米粒子的表面形成蛋白电晕。这一电晕可以被称为动态光散射技术检测。研究人员发现当癌细胞存在时，他们可以“消灭”血液中的IgG，这个特定的交互反应会被黄金纳米粒子检测到。

早前我们已经用动物和人的血液样本进行了我们的研究，现在这项研究用动物模型和人体组织样本证实了我们的成果。如果一切顺利的话，在两到三年内就可以开始临床试验。研究人员希望在五年内该技术就可以被医师用于诊断。

四年前，检测反应的系统就已被发现。它被称为纳米功能动态光散射法（NanoDLSay），它被世界各地的许多研究人员用于从血液中检测癌细胞，从水中检测铅等。

研究者正在寻找资金资助下一步研究，国家科学基金会和佛罗里达州卫生班克黑德科莱基金会资助了大量的基础研究去开发新的技术。

doi:10.1186/1479-5876-10-44
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Developing a nanoparticle test for prostate cancer scoring

Qun Huo1*, Sally A Litherland2, Shannon Sullivan1, Hillari Hallquist1, David A Decker2 and Inoel Rivera-Ramirez2

Background

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.

Method

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.

Results

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.

Conclusion

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.