Serum proteomic profiling using SELDI-Tof MS can distinguish between androgen sensitive and androgen resistant prostate cancer patients

Abstract

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Introduction: Most patients with metastatic prostate cancer (80-90%) will initially respond to hormonal therapy. However, nearly all patients will develop hormone resistant disease and 80% will die within five years. Our goal was to use serum proteomic profiling to identify a signature for hormone resistant disease. Methods: Serum was obtained from 20 patients with androgen sensitive disease and from a separate cohort of 20 patients with androgen insensitive disease. These 40 serum samples were then analyzed using Surface Enhanced Laser Desorption Ionization-Time of Flight (SELDI-Tof) mass spectrometry. Serum was applied to IMAC30 ProteinChip Arrays and the mass range profiled was from 0-50,000 daltons. Results: Using the CiphergenExpress Data Manager software, we were able to identify several candidate biomarkers that could distinguish between hormone sensitive and hormone resistant disease. The most pronounced area of differentiation was between 5,000-8,000 daltons. Heat maps clearly show the difference in protein expression in this area. When p-value calculations were performed, there were 140 peaks that had values ≤ 4.8 x 10^-7. Between 1,300-40,000 daltons, there were 217 peaks that both groups had in common. Conclusion: SELDI-Tof MS can be used to distinguish between prostate cancer patients with hormone sensitive disease and those who will develop hormone resistant disease. From this data we hope to identify the proteins that drive the development of hormone refractory disease.