Proteomics of Breast Cancer

Abstract

Progresses in screening, early diagnosis, prediction of aggressiveness and of therapeutic response or toxicity, and identification of new targets for therapeutic will improve survival of breast cancer. These progresses will likely be accelerated by the new proteomic techniques. In this review, we describe the different techniques currently applied to clinical samples of breast cancer and the most important results obtained with the two most popular proteomic approaches in translational research (tissue microarrays and SELDI-TOF). Molecular & Cellular Proteomics 5:1772-1786, 2006.Worldwide, breast cancer is one of the most frequent and deadly cancers. Although the survival of patients has increased over the last decades in relation with screening programs and postoperative adjuvant systemic therapies (hormone therapy and chemotherapy), many patients die from metastatic relapse. Breast cancer is a complex disease. Accumulation of numerous and often unknown molecular alterations causes cell proliferation, genetic instability, and acquisition of an increasingly invasive and resistant phenotype. The combinatorial origin and the heterogeneity of malignant cells and the variability of the host background create molecularly distinct subgroups of tumors endowed with different phenotypes and clinical outcomes. This heterogeneity is only partially apprehended by the clinicopathological parameters currently used by clinicians, hampering the selection of the most appropriate diagnostic or therapeutic strategy for each case. In addition, current cytotoxic drugs do not differentiate between cancerous and normal cells, causing sometimes disastrous adverse effects. Major efforts aim at characterizing the heterogeneity of the disease by defining more reliable diagnostic/prognostic factors and at developing molecular therapies selectively targeting the tumor cells.For some decades, the study of molecular alterations has successfully elucidated some mechanisms of mammary oncogenesis and identified key genes such as ERBB2, TP53, CCND1, BRCA1, and BRCA2. It has also allowed considerable therapeutic progress by targeting hormonal receptors and ERBB2/HER2 receptor. Today high throughput molecular typing provides an unprecedented opportunity to tackle the combinatory aspect and the complexity of breast cancer. A combination of markers (molecular signature) will probably be more sensitive and specific than a single molecular marker to reflect the actual heterogeneity of disease; more reliable for screening, diagnosis, prognosis, and prediction of therapeutic response; and more useful to find new therapeutic targets. The first large scale techniques applied to the cancer field were DNA microarrays for mRNA expression profiling (1). Several studies have demonstrated the clinical potential of this approach, notably by identifying new biologically relevant and prognostic subclasses of breast cancer unidentifiable by conventional means (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). With the recent development of similar technologies at the DNA...

Clinical Proteomics of Breast Cancer

“…In this area another technique which has just started to be used is the forward and reverse phase protein microarray method, which has made it possible to work with tissue lysates, interstitial fluids and serum samples. However, the limiting aspect in all these array methods is that, the analyses are limited to those performed with known antibodies [9]. …”

Quantitative mass spectrometry of urinary biomarkers

“…It significantly reduces time of analysis and increase reproducibility. After quantification analysis protein spots are extracted from the gel and identified by mass spectrometry (peptide mass fingerprinting) [38]. Matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry and electrospray ionization (ESI)-MS are most often used for the identification of the extracted proteins.…”

Proteomics: Emerging analytical techniques

“…Advantage of this technique involves high throughput via automation and requires minimal sample preparation and the limitation is no direct identification of proteins and sensitive to high molecular weight proteins [56]. The application of SELDI TOF-MS technology is not limited to studies of ovarian, breast, pancreatic and prostate cancers .It has also been used in obtaining proteomic patterns for the diagnosis of bladder cancer from urine samples and cervical cancer from laser capture micro dissected captured cell lysates from tissue samples .Cerebrospinal fluid (CSF) was used in finding and monitoring biomarkers for Alzheimer's disease [54]. In one of the study, surfaceenhanced laser desorption/ionization time-offlight mass spectrometry (SELDI-TOF-MS) was used to analyze proteins associated with T-cell senescence in order to identify potential biomarkers.…”