An efficient biomarker panel for diagnosis of breast cancer using surface-enhanced laser desorption ionization time-of-flight mass spectrometry

Abstract

Abstract. Breast cancer (BC) is the most frequently diagnosed cancer that affects women worldwide. Early detection of BC is important to improve survival rates and decrease mortality. The aim of the present study was to investigate serum biomarkers using surface-enhanced laser desorption ionization time-offlight mass spectrometry (SELDI-TOF-MS) to distinguish patients with BC from the healthy population and patients with benign breast diseases (BBDs). A total of 62 patients with invasive ductal carcinoma, as confirmed by histopathology, and 47 non-cancerous individuals (NCIs) [16 healthy controls (HCs) and 31 patients with BBD] were enrolled in the present study. Serum protein profiles were determined by SELDI-TOF-MS using an immobilized metal affinity capture array. Serum from patients with BC were compared with that from the HC group using univariate and multivariate statistical analyses. A total of 118 clusters were generated from the individual serum. Univariate analysis revealed that 5 peaks were significantly downregulated (m/z 1, 452, 2,670, 3,972, 5,354 and 5,523; P<0.001) and 4 were upregulated (m/z 6,850, 7,926, 8,115 and 8,143; P<0.001) in patients with BC compared with the HC group. A comparison of patients with BC and patients with BBD revealed an additional 9 protein peaks. Among these, 3 peaks (m/z 3,972, 5,336 and 11,185) were significantly downregulated and 6 peaks (m/z 4, 062, 4,071, 4,609, 6,850, 8,115 and 8,133) were significantly upregulated. A total of 3 peaks [mass-to-change ratio (m/z) 3,972, 6,850 and 8,115 (BC2)] were common in both sets. The results of the present study suggest that a 4 protein peak set [m/z 3,972, 6,850 and 8,115 (BC2) and 8,949 (BC3)] could be used to distinguish patients with BC from NCI. IntroductionBreast cancer (BC) is among the most frequent cancers in women in worldwide, and is the second leading cause of cancer-related mortality in women (1). Breast cancer may generally spread to distant locations, which affects curability of the cancer (2). Therefore, accurate and early detection of BC, particularly when pre-symptomatic, is a crucial factor in attaining a higher survival rate and improved prognosis for patients (3). Mammography is a generally preferred method in the detection of BC; however, in young women and women with dense breast tissue, mammographic screening may be less sensitive (4). In these cases, magnetic resonance imaging, an alternative screening approach, may be more sensitive than mammography (5). Blood-based screening tests would be cost-effective and efficient as an application for large-scale screenings. Studies on the specific molecular targets (oncogenes, tumor suppressor genes, growth factors, tumor antigens or other gene products) in BC make possible the application of blood-based screening approaches for BC. Further improvements in protein expression analysis and proteomics methods have led to the development of serum based diagnostics and prognostics for many types of cancer (6). One of these methods, surface-enhanced laser desorp...

Recent Discoveries of Macromolecule- and Cell-Based Biomarkers and Therapeutic Implications in Breast Cancer

“…Others are the combination of vascular endothelial growth factor (VEGF) with CA 15–3 [ 84 ] and the combined human anterior gradient (AGR) 2 and AGR3 biomarker panel [ 85 ]. In addition, CA15-3 was also included in the diagnostic panel consisting of four protein peaks [m/z 3972, 6850, 8115 (Bc2), and 8949 (Bc3)] utilized to differentiate 62 breast cancer patients with invasive ductal carcinoma from 16 healthy controls and 31 patients with benign breast diseases [ 87 ]. Notably, the resultant four peak panel, together with CA15-3, was proven to show high sensitivity and specificity for breast cancer diagnosis.…”

MALDI-TOF MS Analysis of Serum Peptidome Patterns in Cervical Cancer

“…Mass spectrometry is an effective tool for detecting protein and peptide expression in biological fluid [ 15 ] and has gained interest in developing biomarker panels [ 16 ]. Peptides play important roles in several physiological processes, including metabolic products, hormones, and proteolytic enzymes [ 17 ].…”

“…For instance, peptides with m / z values of 1310, 2135, 2411, 2585, 3591, 3973, and 4299 were differentially expressed in healthy subjects, patients with pancreatic cancer, and patients with chronic pancreatitis. In contrast, the peaks at m / z 1209, 1258, 1276, 1448, 1544, 1614, and 1685 were only expressed in healthy subjects [ 16 , 27 ]. Similarly, peptide fingerprints have been used to distinguish between esophageal adenocarcinoma, Barrett’s esophagus, and high-grade dysplasia in healthy subjects.…”

“…Peptidomic pattern analysis has been widely applied in diagnostic tests for gastric, ovarian, hepatic, and breast cancer [24][25][26]. In the ovarian cancer serum, peaks at m/z 5486, 5643, 5253, 8149, 16,450,8054,11,650,3933,7773, and 4560 were more highly expressed in ovarian cancer samples than in healthy samples. However, peaks at m/z 8943, 13,720, 6440, 8142, 6890, 8700, 8575, 13,980, 6369, 4348, and 3260 were lower in ovarian cancer.…”