Application of mass spectrometry to the discovery of biomarkers for detection of prostate cancer

Abstract

There has been an impressive emergence of mass spectrometry based technologies applied toward the study of proteins. Equally notable is the rapid adaptation of these technologies to biomedical approaches in the realm of clinical proteomics. Concerted efforts toward the elucidation of the proteomes of organ sites or specific disease state are proliferating and from these efforts come the promise of better diagnostics/prognostics and therapeutic intervention. Prostate cancer has been a focus of many such studies with the promise of improved care to patients via biomarkers derived from these proteomic approaches. The newer technologies provide higher analytical capabilities, employ automated liquid handling systems, fractionation techniques and bioinformatics tools for greater sensitivity and resolving power, more robust and higher throughput sample processing, and greater confidence in analytical results. In this prospects, we summarize the proteomic technologies applied to date in prostate cancer, along with their respective advantages and disadvantages. The development of newer proteomic strategies for use in future applications is also discussed.

Lectin Capture Strategies Combined with Mass Spectrometry for the Discovery of Serum Glycoprotein Biomarkers

“…Serum protein expression profiling using time-of-flight mass spectrometry approaches to identify biomarkers of disease has reached a nexus of technology development, clinical study design, and bioinformatics. Following a period of promising initial work using MALDI and SELDI mass spectrometry (1)(2)(3)(4), new strategies to increase the utility of this approach for clinical biomarker assay development are needed (5,6). Largely using simple chemical affinity beads or surfaces to decrease the sample complexities, these methods offer an automated, sensitive technique that consumes small amounts of clinical sample with relatively high throughput (2,(7)(8)(9).…”

CE – a multifunctional application for clinical diagnosis

“…Urine has been used for diagnosis of other genitourinary diseases, including cancer [168], similarly as with samples of plasma or serum diseases [162,[169][170][171][172][173]. Theodorescu et al [160] described and validated urinary markers of urothelial carcinoma based on the analysis of urine samples from 46 patients and 33 healthy volunteers by CE-MS.…”

“…Urine is easily collected in large quantities in a noninvasive manner and its composition reflects health status of the kidney [134,138,[153][154][155][156][157], the bladder [158][159][160], the prostate [135,161,162] and vascular system [163]. Urine samples collected in a sterile fashion are stable as compared to serum or plasma [137,164].…”

The use of proteomics to identify novel therapeutic targets for the treatment of disease

“…cardiovascular conditions, as well as the identification of novel therapeutic opportunities and investigations to improve our understanding of the underlying mechanisms of disease. Proteomics has been particularly exploited in several aspects of cancer research, for example breast (current literature review by Bertucci et al (2006) and Hudelist et al (2006)), ovarian (as reviewed by Boyce & Kohn (2005) and Tchabo et al (2005)) and prostatic cancer (summarized by Ornstein & Tyson (2006) and Semmes et al (2006)). Studies have been carried out in an attempt to improve our understanding of the aberrant cellular mechanisms involved in carcinoma development, the occurrence of chemotherapy-resistant tumours, and the identification of diagnostic and prognostic markers to further clarify cancer progression.…”