The importance of protein profiling in the diagnosis and treatment of hematologic malignancies

Abstract

Proteins are important targets in cancer research because malignancy is associated with defects in cell protein machinery. Protein profiling is an emerging independent subspecialty of proteomics that is rapidly expanding and providing unprecedented insight into biological events. Quantitative assessment of protein levels in hematologic malignancies seeks a comprehensive understanding of leukemiaassociated protein patterns for use in aiding diagnosis, follow-up treatment, and the prediction of clinical outcomes. Many recently developed high-throughput proteomic methods can be applied to protein profiling. Herein the importance of protein profiling, its exploitation in leukemia research, and its clinical usefulness in the treatment and diagnosis of various cancer types, and techniques for determining changes in protein profiling are reviewed. (Turk J Hematol 2011; 28: 1-14) Key words: Hematologic malignancies, leukemia, proteomics, protein profiling Received: November 24, 2010 Accepted: January 19, 2011 ÖzetMalignitelerde proteinlerin hücresel mekanizmalarında meydana gelen bozukluklardan dolayı, proteinler kanser araştırmaları için önemli hedeflerdir. Proteomiksin alt uzmanlık dalı olarak ortaya çıkan ve bağımsız bir alan olan protein profilleme biyolojik olaylara farklı bir bakış açısı sağlamak amacıyla hızla gelişmektedir. Hematolojik malignitelerdeki protein düzeylerinin kantitatif olarak değerlendiril-mesi, teşhise yardımcı olması, tedavinin izlenmesi ve klinik sonuçların tahmininde mükemmel bir yaklaşım olması nedeni ile lösemi ile ilgili protein modellerinin kapsamlı bir şekilde incelenmesini amaçlamaktadır. Son dönemlerde geliştirilen yüksek verimli yöntemler protein profillemede kullanıla-bilir. Bu makalede, protein profillemenin önemi, lösemi araştırmalarındaki rolü, çeşitli kanser tiplerinin tanısı ve tedavisi için klinik kullanımları ve protein profilindeki değişikliklerin belirlenmesinde kullanılan teknikler değerlendirilmiştir.

Salivary protein markers: a noninvasive protein profile-based method for the early diagnosis of oral premalignancy and malignancy

“…No premalignant cases were investigated by Hu et al 62 Xie et al 63 have identified proteins in cells separated from saliva from four subjects with oral squamous cell carcinoma of tongue only and have not provided any diagnostic techniques. Almost all studies were done by mass spectroscopic techniques with the inherent disadvantages pointed out by Mohamed et al 60 The present study clearly shows that our technique of HPLC-LIF protein profiling-PCA pattern analysis of the profiles can provide a noninvasive, relatively fast, and sensitive method for screening for early detection. The same technique can, obviously, be used for monitoring the effectiveness of therapy and follow up for early detection of any regression after apparent cure.…”

“…59,60 The reversed phase HPLC with ultra-sensitive LIF detection has been suggested as the best technique for diagnostic applications of protein profiling due to its superior resolution, high-time efficiency, high-detection capacity, and sensitivity. 60 The combination of the highly sensitive LIF (which has advantages such as limited stray light effects, low background and accurate focusing capacity of the excitation source on to the micro-bore capillary leading to the excitation of picoliter amounts of samples without any loss of excitation energy etc.) and highly efficient HPLC enables easy detection of the ultra trace biomolecules in complex physiological samples.…”

A Comparison of Protein Profiles of Cervical Tissue Homogenate, Exfoliated Cells from Cervix and Serum in Normal and Cervical Malignancy Conditions

“…For example, the albumin peak, in 20 mL of 500 times diluted serum gives a signal of .1 V. The noise level in our system is 0.001 V, and this gives a limit of detection (in these runs) of a few femtomoles. We have shown (10)(11)(12)(13)(14)(15)(16)(17) that the sensitivity of the system can be increased by 2-3 orders of magnitude, if necessary, by appropriate choice of experimental parameters (higher laser power, multi-passing laser, collecting more fluorescence with better optics, etc.) and detection system (higher PMT voltage, more signal amplification, use of band pass filters in place of monochromator, etc.).…”

Ultra-sensitive high performance liquid chromatography–laser-induced fluorescence based proteomics for clinical applications

“…Several groups are working at present in this area using different techniques like 2-D gel electrophoresis, MALDI-TOF mass spectrometry, HPLC-MS, SELDI-MS, Bio-bar codes, and HPLC-LIF. Each of these methods has got its own advantages and disadvantages as has been pointed out earlier [14].…”