The Value of Serum Biomarkers (Bc1, Bc2, Bc3) in the Diagnosis of Early Breast Cancer

Atahan, Kemal; Küpeli, Hakan; Gür, Serhat; Yiğitbaşı, Türkan; Baskın, Yasemin; Yiğit, Seyran; Deniz, Mehmet Mehdi; Çökmez, Atilla; Tarcan, Ercüment

doi:10.7150/ijms.8.148

Cited by 14 publications

(12 citation statements)

References 34 publications

(27 reference statements)

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“…Surface-enhanced laser desorption ionization time-of-flight mass spectrometry results for BC and HC groups. (8,9). The peaks at m/z 3,972 and 6,850 may therefore be novel candidate markers for distinguishing patients with BC from NCI.…”

Section: Resultsmentioning

confidence: 99%

“…Table III). Of these, the protein peak at 8,115 Da (BC2) was one of the previously defined biomarkers of BC (8,9). (Table IV).…”

Section: Resultsmentioning

confidence: 99%

“…Decreases in BC1 and increased expression of BC2 and BC3 in patients with BC have been reported in several studies (22,26,27). BC2 and BC3 have also been Table III reported to possess independent diagnostic merit to distinguish between malignant disease, benign disease and control groups (9). BC3 was therefore included in the protein panel for analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Although certain biomarkers may be used to identify BC, few of them have been validated for clinical use. Previous studies have reported a number of potential serum biomarkers that may be used to diagnose BC; BC1 (4.3 kDa), BC2 (8.1 kDa) and BC3 (8.9 kDa) (8,9 are as follows: BC1, inter-α-trypsin inhibitor heavy chain H4; BC2, C3a des-arginine-C terminal truncated peptide; and BC3, C3a des-arginine (10). A number of other potential biomarkers have been identified and demonstrated to have high diagnostic accuracy (7,11,12).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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...

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Section: Resultsmentioning

confidence: 99%

“…Table III). Of these, the protein peak at 8,115 Da (BC2) was one of the previously defined biomarkers of BC (8,9). (Table IV).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…Therefore, CA15-3 is the most widely used biomarker for monitoring BC and for the early diagnosis of BC metastasis but not for the diagnosis of BC [3]. This situation has impeded the development of complex biomarkers for the effective early detection of BC due to its high heterogeneity [4]. By this token, when the two autoantibody biomarkers heterogeneous nuclear ribonucleoprotein F (hnRNPF) and ferritin heavy chain (FTH1), identified by serological analysis of recombinant cDNA expression libraries (SEREX), were analyzed in combination with serum CA15-3 values, the optimal sensitivity and specificity were significantly improved [5].…”

Section: Introductionmentioning

confidence: 98%

Identification of a panel of complex autoantigens (LGALS3, PHB2, MUC1, and GK2) in combination with CA15-3 for the diagnosis of early-stage breast cancer

et al. 2015

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Currently, there is no effective single antigen and there are only a very limited number of complex antigens for the diagnosis of early-stage breast cancer (BC). In this study, we used serological analysis of recombinant cDNA expression libraries (SEREX) in combination with phage display technology to screen complex autoantigens from the sera of BC patients. The cDNA expression library was constructed using tissue samples of three patients with BC at as early as stage T1N0M0. The serum samples of ten patients, including the three patients who provided tissue samples, as well as five healthy human subjects as controls were used to screen the library. All seven autoantigens were identified from the library by four rounds of screening and matched the existing genes after a blast search using NCBI-BLAST. Then, the expression conditions of the autoantibodies of the seven autoantigens and anti-CA15-3 in the sera from 100 BC patients and 50 healthy donors were examined by gray values. The data were analyzed by the area under the receiver operating characteristic (ROC) curve and logistic regression diagnostic models. In the end, a panel of complex autoantigens consisting of B11 (LGALS3), B18 (PHB2), B119 (MUC1), B130 (GK2), and CA15-3, which had a sensitivity of 87 % and a specificity of 76 %, were identified. The area under the curve (AUC) of the complex antigens was 0.872, which is significantly greater than that of anti-CA15-3 alone (AUC = 0.634) for the diagnosis of BC. Thus, this panel of complex antigens provides a promising strategy for the diagnosis of early-stage BC.

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Proteomics analysis of human breast milk to assess breast cancer risk

et al. 2018

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Detection of breast cancer (BC) in young women is challenging because mammography, the most common tool for detecting BC, is not effective on the dense breast tissue characteristic of young women. In addition to the limited means for detecting their BC, young women face a transient increased risk of pregnancy-associated BC. As a consequence, reproductively active women could benefit significantly from a tool that provides them with accurate risk assessment and early detection of BC. One potential method for detection of BC is biochemical monitoring of proteins and other molecules in bodily fluids such as serum, nipple aspirate, ductal lavage, tear, urine, saliva and breast milk. Of all these fluids, only breast milk provides access to a large volume of breast tissue, in the form of exfoliated epithelial cells, and to the local breast environment, in the form of molecules in the milk. Thus, analysis of breast milk is a non-invasive method with significant potential for assessing BC risk. Here we analyzed human breast milk by mass spectrometry (MS)-based proteomics to build a biomarker signature for early detection of BC. Ten milk samples from eight women provided five paired-groups (cancer versus control) for analysis of dysregulatedproteins: two within woman comparisons (milk from a diseased breast versus a healthy breast of the same woman) and three across women comparisons (milk from a woman with cancer versus a woman without cancer). Despite a wide range in the time between milk donation and cancer diagnosis (cancer diagnosis occurred from 1 month before to 24 months after milk donation), the levels of some proteins differed significantly between cancer and control in several of the five comparison groups. These pilot data are supportive of the idea that molecular analysis of breast milk will identify proteins informative for early detection and accurate assessment of BC risk, and warrant further research. Data are available via ProteomeXchange with identifier PXD007066.

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The Value of Serum Biomarkers (Bc1, Bc2, Bc3) in the Diagnosis of Early Breast Cancer

Cited by 14 publications

References 34 publications

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

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

Identification of a panel of complex autoantigens (LGALS3, PHB2, MUC1, and GK2) in combination with CA15-3 for the diagnosis of early-stage breast cancer

Proteomics analysis of human breast milk to assess breast cancer risk

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