ABSTRACT
BACKGROUND: Currently used CA15-3 and CEA have found their clinical application particularly in the follow-up of patients with advanced disease. Novel biomarkers are urgent, especially for improving early diagnosis as well as for discriminating between benign and malignant disease. PATIENTS AND METHODS: In the present study, we used a proteomic approach based on surface-enhanced laser desorption/ionization-time of flight-mass spectrometry screening with the aim of identifying differentially expressed 2-30 kDa proteins in plasma of patients with malignant (65 cases) and benign (88 cases) breast lesions with respect to 121 healthy controls. RESULTS: We found that the most promising SELDI peaks were those corresponding to hepcidin-25 and ferritin light chain. We evaluated the capability of these peaks in predicting malignant and benign breast lesions using the area under the receiver operating characteristic curve (AUC). The results showed a good capacity to predict malignant breast lesions for hepcidin-25 [AUC: 0.82; 95% confidence interval (CI) 0.75-0.90] and ferritin light chain (AUC: 0.86; 95% CI 0.79-0.92). Conversely, a weak and satisfactory capability to predict benign breast lesion was observed for hepcidin-25 (AUC: 0.63; 95% CI 0.41-0.85) and ferritin light chain (AUC: 0.73; 95% CI 0.49-0.97). A significant association between HER2 status and hepcidin-25 was observed and the distribution of transferrin and ferritin were found significantly different in patients with breast cancer when compared with that of controls. CONCLUSIONS: This study provides evidence that hepcidin and ferritin light chain level in plasma may be of clinical usefulness to predict malignant and benign disease with respect to healthy controls.
Subject(s)
Biomarkers, Tumor/blood , Breast Neoplasms/blood , Breast Neoplasms/diagnosis , Ferritins/blood , Hepcidins/blood , Adolescent , Adult , Aged , Case-Control Studies , Early Detection of Cancer , Female , Humans , Middle Aged , ROC Curve , Young AdultABSTRACT
OBJECTIVES: Breast cancer is the most common form of cancer affecting women, and the strongest risk factor remains family history. Although screening in asymptomatic women seems able to reduce breast-cancer related mortality, it is of limited usefulness in young women and patients with familial breast cancer syndrome. New diagnostic tools useful for breast cancer management are urgently needed. The aim of the present paper is to look for new candidate tumor markers useful for diagnosis in these patients. DESIGN AND METHODS: In this prospective study 292 serum samples (100 from healthy people, 100 from sporadic breast cancer patients and 92 from familial breast cancer patients) were analyzed by SELDI-TOF-MS. All samples both from cancer patients and healthy subjects were run in duplicate and randomly spotted on CM10 and IMAC30 protein chip array. Data were analyzed using the expression differential mapping (EDM) tool, decisional tree and multivariate analysis. A further in silico investigation was performed in order to hypothesize the identity of evidenced peptides. RESULTS: EDM highlighted thirteen and sixteen significant differentially expressed peaks by CM10 and IMAC30 protein chip respectively. Subsequent analysis showed that two peaks at m/z 11730 and 5066 were differentially expressed in sporadic and familial breast cancer patients respectively, while a peak at m/z 8127 was overexpressed only in familial breast cancer patients. The diagnostic power of protein peaks was tested by decisional tree; sensitivity and specificity ranged from 17% to 91.67%. CONCLUSIONS: We show that the serum profile of familial breast cancer patients was different when compared with that of sporadic breast cancer patients. We hypothesized the identity of the most significant peaks, and further studies are now planned in order to definitively establish the identity.
Subject(s)
Biomarkers, Tumor/blood , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Genetic Predisposition to Disease , Proteomics/methods , Blood Proteins/analysis , Breast Neoplasms/blood , Case-Control Studies , Early Detection of Cancer , Female , Humans , Middle Aged , Multivariate Analysis , Neoplasm Grading , Prospective Studies , Protein Array Analysis , Sensitivity and Specificity , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Statistics, NonparametricABSTRACT
OBJECTIVES: The purpose of this study was to evaluate the efficacy of a protein-based pattern in serum previously determined by MALDI-TOF-MS (Matrix Assisted Laser Desorption Ionization-Time of Flight) and considered potentially useful for prediction of clinical outcome of EGFR (epidermal growth factor receptor) TKIs (tyrosine kinase inhibitors) treated patients. DESIGN AND METHODS: We generated SELDI-TOF (Surface Enhanced Laser Desorption Ionization-Time of Flight) spectra in sera of 11 advanced NSCLC treated with Gefitinib. We detected the clusters with m/z 5843, 11445, 11529, 11685, 11759 and 11903 which were previously reported to be potential predictors of response to Gefitinib treatment. RESULTS: Four cluster peaks with m/z 5843, 11445, 11529, 11685 corresponded to SAA (serum amyloid A) protein on the basis on their calculated molecular weight, peptide fingerprinting and antibodies recognition. CONCLUSIONS: We confirm that several proteins already reported were isoforms of SAA but further studies are in development in order to evaluate the predictive value of such algorithm.
