Serum Proteomic Analysis Identifies a Highly Sensitive and Specific Discriminatory Pattern in Stage 1 Breast Cancer

Belluco, Claudio; Petricoin, Emanuel F.; Mammano, Enzo; Facchiano, Francesco; Ross-Rucker, Sally; Nitti, Donato; Maggio, C. Di; Liu, Chenwei; Lise, Mario; Liotta, Lance A.; Whiteley, Gordon

doi:10.1245/s10434-007-9354-3

Cited by 79 publications

(68 citation statements)

References 25 publications

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“…A similar use of SELDI-TOF has been published previously, further suggesting that protein profiling can be used to diagnose breast cancer (Li et al, 2002(Li et al, , 2005 Belluco et al (2007) reported excellent capability of their sevenpeak classifier to discriminate serum from stage 1 breast cancer patients from that of controls in an independent cohort. However, and importantly, none of the seven protein peaks were structurally identified.…”

Section: Discussionmentioning

confidence: 57%

Serum protein signature may improve detection of ductal carcinoma in situ of the breast

et al. 2009

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Ductal carcinoma in situ (DCIS) of the breast is part of a spectrum of preinvasive lesions that originate within normal breast tissue and progress to invasive breast cancer. The detection of DCIS is important for the reduction of mortality from breast cancer, but the diagnosis of preinvasive breast tumors is hampered by the lack of an adequate detection method. To identify the changes in protein expression during the initial stage of tumorigenesis and to identify the presence of new DCIS markers, we analysed serum from 60 patients with breast cancer and 60 normal controls using mass spectrometry. A 23-protein index was generated that correctly distinguishes the DCIS and control groups with sensitivities and specificities in excess of 80% in two independent cohorts. Two candidate peptides were purified and identified as platelet factor 4 (PF-4) and complement C3a desArg anaphylatoxin (C3a desArg ) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In an independent serum set of 165 patients, PF-4 and C3a desArg were significantly upregulated in DCIS compared with non-cancerous controls, as validated using western blot and enzyme-linked immunosorbent assay. We conclude that our serum protein-based test, used in conjunction with image-based screening practices, could improve the sensitivity and specificity of breast cancer detection.

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Section: Discussionmentioning

confidence: 57%

Serum protein signature may improve detection of ductal carcinoma in situ of the breast

et al. 2009

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“…This is highlighted by a study of our group [38], in which the potential markers for breast cancer and lymph node status, reported by Vlahou et al [39] and Laronga et al [34], respectively, could not be confirmed following analysis of an independent sample set. In contrast, Belluco et al [40] report excellent performance of their seven-peak classifier (not structurally identified) following validation by an independent sample set analysed 14 months after their initial discovery study. Li et al [41] observed three serum peaks to distinguish patients from controls: one (4.3 kDa) decreased and two (8.1 and 8.9 kDa) increased in patients.…”

Section: Protein Profiling Of Serum and Plasmamentioning

confidence: 90%

Clinical proteomics in breast cancer: a review

Gast

Schellens

Beijnen

2008

Breast Cancer Res Treat

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Breast cancer imposes a significant healthcare burden on women worldwide. Early detection is of paramount importance in reducing mortality, yet the diagnosis of breast cancer is hampered by the lack of an adequate detection method. In addition, better breast cancer prognostication may improve selection of patients eligible for adjuvant therapy. Hence, new markers for early diagnosis, accurate prognosis and prediction of response to treatment are warranted to improve breast cancer care. Since proteomics can bridge the gap between the genetic alterations underlying cancer and cellular physiology, much is expected from proteome analyses for the detection of better protein biomarkers. Recent technical advances in mass spectrometry, such as matrix-assisted laser desorption/ ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and its variant surface-enhanced laser desorption/ ionisation (SELDI-) TOF MS, have enabled highthroughput proteome analysis. In the current review, we give a comprehensive overview of the results of expression proteomics (i.e. protein profiling) research performed in breast cancer using these two platforms. Many protein peaks have been reported to bear significant diagnostic, prognostic or predictive value, however, only few candidate markers have been structurally identified yet. In addition, although of pivotal importance in preventing overfitting of data and systematic bias by pre-analytical parameters, validation of biomarker candidates by other, quantitative, methods and/or in new populations is very limited. Moreover, none of the identified candidate biomarkers has been investigated for their utility as breast cancer markers in large, prospective, clinical settings. As such, the candidate biomarkers discussed in this overview have not been validated sufficiently to be used for clinical patient care. Nonetheless, regarding the promising results up to now, MALDI-and SELDI-TOF MS protein profiling studies could eventually fulfil the great promise that protein biomarkers have for improving cancer patient outcome, provided that these studies are performed with adequate statistical power and analytical rigour.

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“…A 3.8 kDa protein, close to m/z 3,972, was reported to be highly sensitive for the diagnosis of BC by Chung et al (12). A number of serumbased candidate biomarkers have been identified in different studies (8,10,22,31). Studies may have some differences in terms of inclusion/exclusion criteria, biologic samples, preparation protocols, arrays and analytical settings, which will affect the reproducibility and robustness of results.…”

Section: Peak Intensity Protein Peaks -------------------------------mentioning

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%

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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Serum Proteomic Analysis Identifies a Highly Sensitive and Specific Discriminatory Pattern in Stage 1 Breast Cancer

Cited by 79 publications

References 25 publications

Serum protein signature may improve detection of ductal carcinoma in situ of the breast

Serum protein signature may improve detection of ductal carcinoma in situ of the breast

Clinical proteomics in breast cancer: a review

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

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