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Neutrophil Biomarkers Can Predict Cardiotoxicity of Anthracyclines in Breast Cancer.
Todorova, Valentina K; Azhar, Gohar; Stone, Annjanette; Malapati, Sindhu J; Che, Yingni; Zhang, Wei; Makhoul, Issam; Wei, Jeanne Y.
Afiliación
  • Todorova VK; Division of Hematology/Oncology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Azhar G; Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Stone A; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Malapati SJ; Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA.
  • Che Y; Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Zhang W; Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA.
  • Makhoul I; Division of Hematology/Oncology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Wei JY; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Int J Mol Sci ; 25(17)2024 Sep 09.
Article en En | MEDLINE | ID: mdl-39273682
ABSTRACT
Doxorubicin (DOX), a commonly used anticancer agent, causes cardiotoxicity that begins with the first dose and may progress to heart failure years after treatment. An inflammatory response associated with neutrophil recruitment has been recognized as a mechanism of DOX-induced cardiotoxicity. This study aimed to validate mRNA expression of the previously identified biomarkers of DOX-induced cardiotoxicity, PGLYRP1, CAMP, MMP9, and CEACAM8, and to assay their protein expression in the peripheral blood of breast cancer patients. Blood samples from 40 breast cancer patients treated with DOX-based chemotherapy were collected before and after the first chemotherapy cycle and > 2 years after treatment. The protein and gene expression of PGLYRP1/Tag7, CAMP/LL37, MMP9/gelatinase B, and CEACAM8/CD66b were determined using ELISA and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of each candidate biomarker. Patients with cardiotoxicity (n = 20) had significantly elevated levels of PGLYRP1, CAMP, MMP9, and CEACAM8 at baseline, after the first dose of DOX-based chemotherapy, and at > 2 years after treatment relative to patients without cardiotoxicity (n = 20). The first dose of DOX induced significantly higher levels of all examined biomarkers in both groups of patients. At > 2 years post treatment, the levels of all but MMP9 dropped below the baseline. There was a good correlation between the expression of mRNA and the target proteins. We demonstrate that circulating levels of PGLYRP1, CAMP, MMP9, and CEACAM8 can predict the cardiotoxicity of DOX. This novel finding may be of value in the early identification of patients at risk for cardiotoxicity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Doxorrubicina / Antraciclinas / Cardiotoxicidad / Neutrófilos Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Doxorrubicina / Antraciclinas / Cardiotoxicidad / Neutrófilos Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza