Surfaced-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) differentiation of serum protein profiles of BRCA-1 and sporadic breast cancer

Stephen Becker, Lisa H. Cazares, Patrice Watson, Henry T. Lynch, O. John Semmes, Richard R. Drake, Christine Laronga

Research output: Contribution to journalArticle

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Abstract

Background: BRCA-1 mutations predispose women to early onset breast cancer, but ∼20% never develop cancer. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) profiling can differentiate protein signatures of cancer and normal subjects. Our objective was to distinguish women with BRCA-1 mutations who developed breast cancer (BRCA-1 Ca) from those who did not (Carrier), normal volunteers (NL), and women with sporadic breast cancer (SBC), using SELDI-TOF. Methods: Baseline serum specimens were obtained from women with BRCA-1 mutations without cancer, SBC, and NL. BRCA-1 women were later divided into two cohorts, pending cancer development. The sera were spotted onto protein chips for SELDI-TOF analysis and analyzed with classification algorithm software. Results: BRCA-1 Ca patients (n = 15) developed cancer within 3 years of baseline, while BRCA-1 carriers (n = 15) were cancer-free in 7 years of follow-up. SELDI-TOF analysis revealed differentially expressed proteins (P <.05) between BRCA-1 Ca, Carrier, and SBC patients (n = 16), such that 13/15 BRCA-1 Ca vs. Carrier women were correctly identified (sensitivity/specificity of 87%/87%) and 14/15 BRCA-1 Ca vs. SBC patients were correctly identified (sensitivity/specificity 94%/100%). Profiles of Carriers resembled NL profiles (n = 16). Conclusions: SELDI-TOF protein profiles from this small pilot study distinguished between women with BRCA-1 Ca, Carriers, and women with SBC. Whether BRCA-1 Ca represents earlier detection of occult cancer or other risk factors is unknown. Follow-up studies with larger numbers and longer follow-up are required to validate these findings but may allow more timely prophylactic or therapeutic strategies.

Original languageEnglish
Pages (from-to)907-914
Number of pages8
JournalAnnals of Surgical Oncology
Volume11
Issue number10
DOIs
StatePublished - 2004

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Blood Proteins
Lasers
Breast Neoplasms
Healthy Volunteers
Neoplasms
Mutation
Sensitivity and Specificity
Protein Array Analysis
Proteins
Serum
Early Detection of Cancer
Mass Spectrometry
Software

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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Surfaced-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) differentiation of serum protein profiles of BRCA-1 and sporadic breast cancer. / Becker, Stephen; Cazares, Lisa H.; Watson, Patrice; Lynch, Henry T.; Semmes, O. John; Drake, Richard R.; Laronga, Christine.

In: Annals of Surgical Oncology, Vol. 11, No. 10, 2004, p. 907-914.

Research output: Contribution to journalArticle

Becker, Stephen ; Cazares, Lisa H. ; Watson, Patrice ; Lynch, Henry T. ; Semmes, O. John ; Drake, Richard R. ; Laronga, Christine. / Surfaced-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) differentiation of serum protein profiles of BRCA-1 and sporadic breast cancer. In: Annals of Surgical Oncology. 2004 ; Vol. 11, No. 10. pp. 907-914.
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title = "Surfaced-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) differentiation of serum protein profiles of BRCA-1 and sporadic breast cancer",
abstract = "Background: BRCA-1 mutations predispose women to early onset breast cancer, but ∼20{\%} never develop cancer. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) profiling can differentiate protein signatures of cancer and normal subjects. Our objective was to distinguish women with BRCA-1 mutations who developed breast cancer (BRCA-1 Ca) from those who did not (Carrier), normal volunteers (NL), and women with sporadic breast cancer (SBC), using SELDI-TOF. Methods: Baseline serum specimens were obtained from women with BRCA-1 mutations without cancer, SBC, and NL. BRCA-1 women were later divided into two cohorts, pending cancer development. The sera were spotted onto protein chips for SELDI-TOF analysis and analyzed with classification algorithm software. Results: BRCA-1 Ca patients (n = 15) developed cancer within 3 years of baseline, while BRCA-1 carriers (n = 15) were cancer-free in 7 years of follow-up. SELDI-TOF analysis revealed differentially expressed proteins (P <.05) between BRCA-1 Ca, Carrier, and SBC patients (n = 16), such that 13/15 BRCA-1 Ca vs. Carrier women were correctly identified (sensitivity/specificity of 87{\%}/87{\%}) and 14/15 BRCA-1 Ca vs. SBC patients were correctly identified (sensitivity/specificity 94{\%}/100{\%}). Profiles of Carriers resembled NL profiles (n = 16). Conclusions: SELDI-TOF protein profiles from this small pilot study distinguished between women with BRCA-1 Ca, Carriers, and women with SBC. Whether BRCA-1 Ca represents earlier detection of occult cancer or other risk factors is unknown. Follow-up studies with larger numbers and longer follow-up are required to validate these findings but may allow more timely prophylactic or therapeutic strategies.",
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T1 - Surfaced-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) differentiation of serum protein profiles of BRCA-1 and sporadic breast cancer

AU - Becker, Stephen

AU - Cazares, Lisa H.

AU - Watson, Patrice

AU - Lynch, Henry T.

AU - Semmes, O. John

AU - Drake, Richard R.

AU - Laronga, Christine

PY - 2004

Y1 - 2004

N2 - Background: BRCA-1 mutations predispose women to early onset breast cancer, but ∼20% never develop cancer. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) profiling can differentiate protein signatures of cancer and normal subjects. Our objective was to distinguish women with BRCA-1 mutations who developed breast cancer (BRCA-1 Ca) from those who did not (Carrier), normal volunteers (NL), and women with sporadic breast cancer (SBC), using SELDI-TOF. Methods: Baseline serum specimens were obtained from women with BRCA-1 mutations without cancer, SBC, and NL. BRCA-1 women were later divided into two cohorts, pending cancer development. The sera were spotted onto protein chips for SELDI-TOF analysis and analyzed with classification algorithm software. Results: BRCA-1 Ca patients (n = 15) developed cancer within 3 years of baseline, while BRCA-1 carriers (n = 15) were cancer-free in 7 years of follow-up. SELDI-TOF analysis revealed differentially expressed proteins (P <.05) between BRCA-1 Ca, Carrier, and SBC patients (n = 16), such that 13/15 BRCA-1 Ca vs. Carrier women were correctly identified (sensitivity/specificity of 87%/87%) and 14/15 BRCA-1 Ca vs. SBC patients were correctly identified (sensitivity/specificity 94%/100%). Profiles of Carriers resembled NL profiles (n = 16). Conclusions: SELDI-TOF protein profiles from this small pilot study distinguished between women with BRCA-1 Ca, Carriers, and women with SBC. Whether BRCA-1 Ca represents earlier detection of occult cancer or other risk factors is unknown. Follow-up studies with larger numbers and longer follow-up are required to validate these findings but may allow more timely prophylactic or therapeutic strategies.

AB - Background: BRCA-1 mutations predispose women to early onset breast cancer, but ∼20% never develop cancer. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) profiling can differentiate protein signatures of cancer and normal subjects. Our objective was to distinguish women with BRCA-1 mutations who developed breast cancer (BRCA-1 Ca) from those who did not (Carrier), normal volunteers (NL), and women with sporadic breast cancer (SBC), using SELDI-TOF. Methods: Baseline serum specimens were obtained from women with BRCA-1 mutations without cancer, SBC, and NL. BRCA-1 women were later divided into two cohorts, pending cancer development. The sera were spotted onto protein chips for SELDI-TOF analysis and analyzed with classification algorithm software. Results: BRCA-1 Ca patients (n = 15) developed cancer within 3 years of baseline, while BRCA-1 carriers (n = 15) were cancer-free in 7 years of follow-up. SELDI-TOF analysis revealed differentially expressed proteins (P <.05) between BRCA-1 Ca, Carrier, and SBC patients (n = 16), such that 13/15 BRCA-1 Ca vs. Carrier women were correctly identified (sensitivity/specificity of 87%/87%) and 14/15 BRCA-1 Ca vs. SBC patients were correctly identified (sensitivity/specificity 94%/100%). Profiles of Carriers resembled NL profiles (n = 16). Conclusions: SELDI-TOF protein profiles from this small pilot study distinguished between women with BRCA-1 Ca, Carriers, and women with SBC. Whether BRCA-1 Ca represents earlier detection of occult cancer or other risk factors is unknown. Follow-up studies with larger numbers and longer follow-up are required to validate these findings but may allow more timely prophylactic or therapeutic strategies.

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