Plasma autoantibodies associated with basal-like breast cancers

Jie Wang, Jonine D. Figueroa, Garrick Wallstrom, Kristi Barker, Jin Park, Gokhan Demirkan, Jolanta Lissowska, Karen Anderson, Ji Qiu, Joshua LaBaer

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: Basal-like breast cancer (BLBC) is a rare aggressive subtype that is less likely to be detected through mammographic screening. Identification of circulating markers associated with BLBC could have promise in detecting and managing this deadly disease. Methods: Using samples from the Polish Breast Cancer study, a high-quality population-based case-control study of breast cancer, we screened 10,000 antigens on protein arrays using 45 BLBC patients and 45 controls, and identified 748 promising plasma autoantibodies (AAbs) associated with BLBC. ELISA assays of promising markers were performed on a total of 145 BLBC cases and 145 age-matched controls. Sensitivities at 98% specificity were calculated and a BLBC classifier was constructed. Results: We identified 13 AAbs (CTAG1B, CTAG2, TP53, RNF216, PPHLN1, PIP4K2C, ZBTB16, TAS2R8, WBP2NL, DOK2, PSRC1, MN1, TRIM21) that distinguished BLBC from controls with 33% sensitivity and 98% specificity. We also discovered a strong association of TP53 AAb with its protein expression (P = 0.009) in BLBC patients. In addition, MN1 and TP53 AAbs were associated with worse survival [MN1 AAb marker HR=2.25, 95% confidence interval (CI), 1.03-4.91; P = 0.04; TP53, HR = 2.02, 95% CI, 1.06-3.85; P = 0.03]. We found limited evidence that AAb levels differed by demographic characteristics. Conclusions: These AAbs warrant further investigation in clinical studies to determine their value for further understanding the biology of BLBC and possible detection. Impact: Our study identifies 13 AAb markers associated specifically with BLBC and may improve detection or management of this deadly disease.

Original languageEnglish (US)
Pages (from-to)1332-1340
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume24
Issue number9
DOIs
StatePublished - Sep 1 2015

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Autoantibodies
Breast Neoplasms
Confidence Intervals
Protein Array Analysis
Disease Management
Case-Control Studies
Enzyme-Linked Immunosorbent Assay
Demography
Antigens
Sensitivity and Specificity
Survival

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Plasma autoantibodies associated with basal-like breast cancers. / Wang, Jie; Figueroa, Jonine D.; Wallstrom, Garrick; Barker, Kristi; Park, Jin; Demirkan, Gokhan; Lissowska, Jolanta; Anderson, Karen; Qiu, Ji; LaBaer, Joshua.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 24, No. 9, 01.09.2015, p. 1332-1340.

Research output: Contribution to journalArticle

Wang, Jie ; Figueroa, Jonine D. ; Wallstrom, Garrick ; Barker, Kristi ; Park, Jin ; Demirkan, Gokhan ; Lissowska, Jolanta ; Anderson, Karen ; Qiu, Ji ; LaBaer, Joshua. / Plasma autoantibodies associated with basal-like breast cancers. In: Cancer Epidemiology Biomarkers and Prevention. 2015 ; Vol. 24, No. 9. pp. 1332-1340.
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abstract = "Background: Basal-like breast cancer (BLBC) is a rare aggressive subtype that is less likely to be detected through mammographic screening. Identification of circulating markers associated with BLBC could have promise in detecting and managing this deadly disease. Methods: Using samples from the Polish Breast Cancer study, a high-quality population-based case-control study of breast cancer, we screened 10,000 antigens on protein arrays using 45 BLBC patients and 45 controls, and identified 748 promising plasma autoantibodies (AAbs) associated with BLBC. ELISA assays of promising markers were performed on a total of 145 BLBC cases and 145 age-matched controls. Sensitivities at 98{\%} specificity were calculated and a BLBC classifier was constructed. Results: We identified 13 AAbs (CTAG1B, CTAG2, TP53, RNF216, PPHLN1, PIP4K2C, ZBTB16, TAS2R8, WBP2NL, DOK2, PSRC1, MN1, TRIM21) that distinguished BLBC from controls with 33{\%} sensitivity and 98{\%} specificity. We also discovered a strong association of TP53 AAb with its protein expression (P = 0.009) in BLBC patients. In addition, MN1 and TP53 AAbs were associated with worse survival [MN1 AAb marker HR=2.25, 95{\%} confidence interval (CI), 1.03-4.91; P = 0.04; TP53, HR = 2.02, 95{\%} CI, 1.06-3.85; P = 0.03]. We found limited evidence that AAb levels differed by demographic characteristics. Conclusions: These AAbs warrant further investigation in clinical studies to determine their value for further understanding the biology of BLBC and possible detection. Impact: Our study identifies 13 AAb markers associated specifically with BLBC and may improve detection or management of this deadly disease.",
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T1 - Plasma autoantibodies associated with basal-like breast cancers

AU - Wang, Jie

AU - Figueroa, Jonine D.

AU - Wallstrom, Garrick

AU - Barker, Kristi

AU - Park, Jin

AU - Demirkan, Gokhan

AU - Lissowska, Jolanta

AU - Anderson, Karen

AU - Qiu, Ji

AU - LaBaer, Joshua

PY - 2015/9/1

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AB - Background: Basal-like breast cancer (BLBC) is a rare aggressive subtype that is less likely to be detected through mammographic screening. Identification of circulating markers associated with BLBC could have promise in detecting and managing this deadly disease. Methods: Using samples from the Polish Breast Cancer study, a high-quality population-based case-control study of breast cancer, we screened 10,000 antigens on protein arrays using 45 BLBC patients and 45 controls, and identified 748 promising plasma autoantibodies (AAbs) associated with BLBC. ELISA assays of promising markers were performed on a total of 145 BLBC cases and 145 age-matched controls. Sensitivities at 98% specificity were calculated and a BLBC classifier was constructed. Results: We identified 13 AAbs (CTAG1B, CTAG2, TP53, RNF216, PPHLN1, PIP4K2C, ZBTB16, TAS2R8, WBP2NL, DOK2, PSRC1, MN1, TRIM21) that distinguished BLBC from controls with 33% sensitivity and 98% specificity. We also discovered a strong association of TP53 AAb with its protein expression (P = 0.009) in BLBC patients. In addition, MN1 and TP53 AAbs were associated with worse survival [MN1 AAb marker HR=2.25, 95% confidence interval (CI), 1.03-4.91; P = 0.04; TP53, HR = 2.02, 95% CI, 1.06-3.85; P = 0.03]. We found limited evidence that AAb levels differed by demographic characteristics. Conclusions: These AAbs warrant further investigation in clinical studies to determine their value for further understanding the biology of BLBC and possible detection. Impact: Our study identifies 13 AAb markers associated specifically with BLBC and may improve detection or management of this deadly disease.

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