Mass Spectroscopy as a Discovery Tool for Identifying Serum Markers for Prostate Cancer

Abstract

Prostate cancer is the second most common malignancy in men, after skin cancer, and the second most common cause of cancer death in men over age 60 years, after lung cancer. This year, ∼198 100 new cases of prostate cancer will be diagnosed in the US, and an estimated 31 500 men will die of prostate cancer (1). Five-year survival is close to 100% when the disease is diagnosed and treated with definitive local therapy while it is still organ-confined, but in approximately one-third of men diagnosed with clinically localized disease, the disease has spread beyond the confines of the prostate at the time of surgery (2)(3). The Food and Drug Administration approved a serum test for prostate-specific antigen (PSA) in the 1980s. With an upper reference limit in serum of 4 μg/L, 67–80% of prostate cancers can be detected, for a positive predictive value of 24% (4)(5). Combining the serum PSA test with a digital rectal examination can improve the positive predictive value (3)(6)(7). Despite the availability of the PSA test and the moderately high compliance with routine testing recommendations, ∼20–30% of prostate cancers are missed by the current early detection protocols. The identification of more accurate serum markers for prostate cancer could improve the current clinical capabilities for cancer detection and may reduce cancer mortality. Proteomics, the large-scale comparison of protein expression patterns, can be used to identify proteins that are associated with disease states such as cancer. These studies have been enhanced by the development of powerful and sensitive new methods, such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF). In this technique, proteins are adsorbed to a solid matrix, desorbed with a pulsed laser beam to produce gas-phase …