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Secretome proteomics reveals candidate non-invasive biomarkers of BRCA1 deficiency in breast cancer.

ABSTRACT: Breast cancer arising in female BRCA1 mutation carriers is characterized by an aggressive phenotype and early age of onset. We performed tandem mass spectrometry-based proteomics of secretomes and exosome-like extracellular vesicles from BRCA1-deficient and BRCA1-proficient murine breast tumor models to identify extracellular protein biomarkers, which can be used as an adjunct to current diagnostic modalities in patients with BRCA1-deficient breast cancer. We identified 2,107 proteins, of which 215 were highly enriched in the BRCA1-deficient secretome. We demonstrated that BRCA1-deficient secretome proteins could cluster most human BRCA1- and BRCA2-related breast carcinomas at the transcriptome level. Topoisomerase I (TOP1) and P-cadherin (CDH3) expression was investigated by immunohistochemistry on tissue microarrays of a large panel of 253 human breast carcinomas with and without BRCA1/2 mutations. We showed that expression of TOP1 and CDH3 was significantly increased in human BRCA1-related breast carcinomas relative to sporadic cases (p = 0.002 and p < 0.001, respectively). Multiple logistic regression showed that TOP1 (adjusted odds ratio [OR] 3.75; 95% confidence interval [95% CI], 1.85 - 7.71, p < 0.001) as well as CDH3 positivity (adjusted OR 2.45; 95% CI, 1.08 - 5.49, p = 0.032) were associated with BRCA1/2-related breast carcinomas after adjustment for triple-negative phenotype and age. In conclusion, proteome profiling of secretome using murine breast tumor models is a powerful strategy to identify non-invasive candidate biomarkers of BRCA1-deficient breast cancer. We demonstrate that TOP1 and CDH3 are closely associated to BRCA1-deficient breast cancer. These data merit further investigation for early detection of tumors arising in BRCA1 mutation carriers.

SUBMITTER: Warmoes M

PROVIDER: S-EPMC5325383 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Secretome proteomics reveals candidate non-invasive biomarkers of BRCA1 deficiency in breast cancer.

Warmoes Marc M Lam Siu W SW van der Groep Petra P Jaspers Janneke E JE Smolders Yvonne H C M YH de Boer Leon L Pham Thang V TV Piersma Sander R SR Rottenberg Sven S Boven Epie E Jonkers Jos J van Diest Paul J PJ Jimenez Connie R CR

Oncotarget 20160901 39

Breast cancer arising in female BRCA1 mutation carriers is characterized by an aggressive phenotype and early age of onset. We performed tandem mass spectrometry-based proteomics of secretomes and exosome-like extracellular vesicles from BRCA1-deficient and BRCA1-proficient murine breast tumor models to identify extracellular protein biomarkers, which can be used as an adjunct to current diagnostic modalities in patients with BRCA1-deficient breast cancer. We identified 2,107 proteins, of which ...[more]

PMID: 27566577

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Secretome proteomics reveals candidate non-invasive biomarkers of BRCA1 deficiency in breast cancer.

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Secretome proteomics reveals candidate non-invasive biomarkers of BRCA1 deficiency in breast cancer.

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