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

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-of-flight 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.

Keywords: biomarker; breast cancer; early diagnosis; proteomics; surface-enhanced laser desorption ionization time-of-flight mass spectrometry.

Figure 1.

All-in-one peptide molecular mass standard for six peptides, including 1084.247-[arginine 8]-vasopressin, 1637.903-somatostatin, 2147.500-dynorphin A, 2933.500-adrenocorticotropic hormone [1–24] human, 3495.941-insulin B-chain (bovine) and 7033.614-hirudin.

Figure 2.

ROC curve for each protein peak identified using SELDI-TOF-MS in patients with breast cancer compared with non-cancerous individuals. Area under curve values were as follows: m/z 3,972, 0.700; m/z 6,850, 0.752; m/z 8,115, 0.732; m/z 8,949, 0.603; CA15-3, 0.762. ROC, receiver operating characteristic; SELDI-TOF-MS, surface-enhanced laser desorption ionization time-of-flight mass spectrometry; CA15-3, carbohydrate antigen 15-3.