Abstract 3628: Predict prostate cancer aggressiveness quantitatively using a nanoparticle test
Authors: Qun Huo
Journal: Cancer Research (2012)

Abstract BACKGROUND: Prostate cancer (PCa) is the most common malignancy and the second leading cause of cancer death in American men. Using digital rectal examination combined with PSA test, most prostate cancer cases are now detected at early stage. However, due to the lack of accurate tests to distinguish aggressive cancer from indolent tumor, prostate cancer is often over-treated. Over-diagnosis and treatment of low risk prostate cancer has serious and long-lasting side effect: as high as 70% of the patients who receive radical prostatectomy treatment will suffer a loss of sexual potency that cannot be remedied by drugs such as sildenafil citrate. Currently the most relevant prognostic factor to predict a patient's risk of death due to PCa 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. METHOD: We report for the first time a gold nanoparticle-serum protein IgG adsorption test that not only can distinguish prostate cancer from normal and benign conditions, but also is capable of predicting the aggressiveness of prostate cancer quantitatively. To conduct the test, a prostate tissue lysate sample is spiked into a human IgG solution and the spiked sample is mixed 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 our study, we discovered that certain tumor-specific molecules can interact with the serum IgG and change the adsorption behavior of IgG to the gold nanoparticles. This change is reflected in the nanoparticle size of the assay solution that is detected by a dynamic light scattering technique. 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. Based on the assay results and various control experiments, a mechanism was proposed to explain the observed differences: IgG protein, either as a monomer or oligomer, causes gold nanoparticle cluster formation when the proteins are adsorbed to the nanoparticles. When tumor tissue lysates are spiked into the IgG solution, the specific binding of tumor-specific molecules with IgG inhibits the crosslinking of the gold nanoparticles, leading to a decreased average particle size of the assay solution. CONCLUSION: The nanoparticle test reported here provides a quantitative measure of the prostate cancer aggressiveness. This test could become a more accurate diagnostic/prognostic tool to assess the prostate tumor aggressiveness than the current diagnostic practices. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3628. doi:1538-7445.AM2012-3628