Biomarkers for Presymptomatic Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients

Valentina K. Todorova, Issam Makhoul, Eric R. Siegel, Jeanne Wei, Annjanette Stone, Weleetka Carter, Marjorie L. Beggs, Aaron Owen, Vicki Klimberg

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Cardiotoxicity of doxorubicin (DOX) remains an important health concern. DOX cardiotoxicity is cumulative-dose-dependent and begins with the first dose of chemotherapy. No biomarker for presymptomatic detection of DOX cardiotoxicity has been validated. Our hypothesis is that peripheral blood cells (PBC) gene expression induced by the early doses of DOX-based chemotherapy could identify potential biomarkers for presymptomatic cardiotoxicity in cancer patients. PBC gene expression of 33 breast cancer patients was conducted before and after the first cycle of DOX-based chemotherapy. Cardiac function was evaluated before the start of chemotherapy and at its completion. Differentially expressed genes (DEG) of patients who developed DOX-associated cardiotoxicity after the completion of chemotherapy were compared with DEG of patients who did not. Ingenuity database was used for functional analysis of DEG. Sixty-sevens DEG (P<0.05) were identified in PBC of patients with DOX-cardiotoxicity. Most of DEG encode proteins secreted by activated neutrophils. The functional analysis of the DEG showed enrichment for immune- and inflammatory response. This is the first study to identify the PBC transcriptome signature associated with a single dose of DOX-based chemotherapy in cancer patients. We have shown that PBC transcriptome signature associated with one dose of DOX chemotherapy in breast cancer can predict later impairment of cardiac function.

Original languageEnglish (US)
Article numbere0160224
JournalPLoS One
Volume11
Issue number8
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Fingerprint

doxorubicin
Biomarkers
breast neoplasms
Doxorubicin
Chemotherapy
biomarkers
drug therapy
Breast Neoplasms
blood cells
Genes
Drug Therapy
Blood Cells
Blood
dosage
Functional analysis
genes
cardiac output
Transcriptome
Gene expression
transcriptome

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Todorova, V. K., Makhoul, I., Siegel, E. R., Wei, J., Stone, A., Carter, W., ... Klimberg, V. (2016). Biomarkers for Presymptomatic Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients. PLoS One, 11(8), [e0160224]. https://doi.org/10.1371/journal.pone.0160224

Biomarkers for Presymptomatic Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients. / Todorova, Valentina K.; Makhoul, Issam; Siegel, Eric R.; Wei, Jeanne; Stone, Annjanette; Carter, Weleetka; Beggs, Marjorie L.; Owen, Aaron; Klimberg, Vicki.

In: PLoS One, Vol. 11, No. 8, e0160224, 01.08.2016.

Research output: Contribution to journalArticle

Todorova, VK, Makhoul, I, Siegel, ER, Wei, J, Stone, A, Carter, W, Beggs, ML, Owen, A & Klimberg, V 2016, 'Biomarkers for Presymptomatic Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients', PLoS One, vol. 11, no. 8, e0160224. https://doi.org/10.1371/journal.pone.0160224
Todorova VK, Makhoul I, Siegel ER, Wei J, Stone A, Carter W et al. Biomarkers for Presymptomatic Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients. PLoS One. 2016 Aug 1;11(8). e0160224. https://doi.org/10.1371/journal.pone.0160224
Todorova, Valentina K. ; Makhoul, Issam ; Siegel, Eric R. ; Wei, Jeanne ; Stone, Annjanette ; Carter, Weleetka ; Beggs, Marjorie L. ; Owen, Aaron ; Klimberg, Vicki. / Biomarkers for Presymptomatic Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients. In: PLoS One. 2016 ; Vol. 11, No. 8.
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