Immune response proteins as predictive biomarkers of doxorubicin-induced cardiotoxicity in breast cancer patients.

Cancer treatment with doxorubicin (DOX) can induce cumulative dose-dependent cardiotoxicity. Currently, there are no specific biomarkers that can identify patients at risk during the initial doses of chemotherapy. The aim of this study was to examine plasma cytokines/chemokines and potential cardiovascular biomarkers for the prediction of DOX-induced cardiotoxicity.

Regulatory perspective on translating proteomic biomarkers to clinical diagnostics.

Issues associated with the translation of complex proteomic biomarkers from discovery to clinical diagnostics have been widely discussed among academic researchers, government agencies, as well as assay and instrumentation manufacturers. Here, we provide an overview of the regulatory framework and type of information that is typically required in order to evaluate in vitro diagnostic tests regulated by the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) at the US Food and Drug Administration (FDA), with the focus on some of the issues specific to protein-based complex tests. Technological points pertaining to mass spectrometry platforms and assessment of potential concerns important for assurance of safety and effectiveness of this type of assays when introduced into clinical diagnostic use, as well as general approaches for evaluating the performance of these devices, are discussed.

Analytical performance of 4 automated assays for measurement of cystatin C.

Background: We evaluated the analytical performance of 4 cystatin C assays (Siemens N Latex on BNII, Roche Tina-quant on Cobas c501, Genzyme on Cobas c501, and Tosoh ST AIA-PACK on Tosoh AIA-600II) according to guidelines published by the Clinical and Laboratory Standards Institute.

Methods: We evaluated total imprecision, limit of detection, and limit of quantification for each assay using patient serum pools and linearity/recovery using serial dilutions of a patient serum pool with cystatin C-free serum. We compared patients (n = 102) using the Siemens assay as a comparison method.

A unique proteolytic fragment of alpha1-antitrypsin is elevated in ductal fluid of breast cancer patient.

By comparison of mass spectra from a small cohort of nipple aspiration fluids (NAF), we previously discovered a panel of five candidate breast cancer biomarkers among them an unidentified 4.7 kD peptide BF5. The purposes of the present study were to verify the presence of BF5 in an independent cohort; to determine the protein identity of BF5; and to provide insight into the biology of BF5 production and elevation in tumor-associated NAF.

Identification of biomarkers for breast cancer in nipple aspiration and ductal lavage fluid.

Purpose: To establish a comprehensive proteomic approach for biomarker discovery and validation in breast fluid.

Experimental Design: A total of 95 specimens from three institutions were used including 10 nipple aspiration fluid (5 stage I/II cancerous breasts and 5 age-matched healthy controls), 42 ductal lavage fluid from 14 patients with unilateral stage I/II cancer (25 from 9 cancerous breasts and 17 from 7 contralateral breasts), and 42 ductal lavage fluid from 14 high-risk women (multiple ducts repeated lavage). Differentially expressed protein/peptides were discovered by proteomic analysis of training sample, using ProteinChip arrays and surface-enhanced laser desorption ionization (SELDI) time-of-flight mass spectrometry, and validated on independently collected testing samples.

Independent validation of candidate breast cancer serum biomarkers identified by mass spectrometry.

Background: We previously selected a panel of 3 breast cancer biomarkers (BC1, BC2, and BC3) from serum samples collected at a single hospital based on their collective contribution to the optimal separation of breast cancer patients and noncancer controls by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The identities and general applicability of these markers, however, were unknown. In this study, we performed protein expression profiling on samples obtained from a second hospital, included a greater number of ductal carcinoma in situ (DCIS) cases, and performed purification and identification of the 2 confirmed markers.

Fatty acid synthase as a tumor marker: its extracellular expression in human breast cancer.

Overexpression of fatty acid synthase (FAS EC 2.3.1.

Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer.

Early detection remains the most promising approach to improve long-term survival of patients with ovarian cancer. In a five-center case-control study, serum proteomic expressions were analyzed on 153 patients with invasive epithelial ovarian cancer, 42 with other ovarian cancers, 166 with benign pelvic masses, and 142 healthy women. Data from patients with early stage ovarian cancer and healthy women at two centers were analyzed independently and the results cross-validated to discover potential biomarkers.

Detection of prostate cancer using serum proteomics pattern in a histologically confirmed population.

Purpose: We retrospectively identified a panel of serum proteins that can discriminate between men with prostate cancer (clinically organ confined) and men with benign prostate disease.

Materials And Methods: A contemporary set of 345 men who had an archival serum sample available were included in this study. The cancer group consisted of 246 men who underwent radical prostatectomy at the Johns Hopkins Hospital between March 1999 and April 2001.

Proteomics and bioinformatics approaches for identification of serum biomarkers to detect breast cancer.

Background: Surface-enhanced laser desorption/ionization (SELDI) is an affinity-based mass spectrometric method in which proteins of interest are selectively adsorbed to a chemically modified surface on a biochip, whereas impurities are removed by washing with buffer. This technology allows sensitive and high-throughput protein profiling of complex biological specimens.

Methods: We screened for potential tumor biomarkers in 169 serum samples, including samples from a cancer group of 103 breast cancer patients at different clinical stages [stage 0 (n = 4), stage I (n = 38), stage II (n = 37), and stage III (n = 24)], from a control group of 41 healthy women, and from 25 patients with benign breast diseases.