Abstract:
RATIONALE:There is a critical need to develop robust, mechanistic strategies to identify patients at increased risk of cancer therapeutics-related cardiac dysfunction (CTRCD). OBJECTIVE:We aimed to discover new biomarkers associated with doxorubicin- and trastuzumab-induced CTRCD using high-throughput proteomic profiling. METHODS AND RESULTS:Plasma, echocardiograms, and clinical outcomes were collected at standardized intervals in breast cancer patients undergoing doxorubicin and trastuzumab cancer therapy. Thirty-one longitudinal plasma samples from 3 cases with CTRCD and 4 age- and cancer-matched controls without CTRCD were processed and analyzed using label-free liquid chromatography-mass spectrometry. From these analyses, 862 proteins were identified from case/control pairs 1 and 2 and 1360 proteins from case/control pair 3. Proteins with a >1.5-fold change in cases compared with controls with a P<0.05 either at the time of CTRCD diagnosis or across all time points were considered candidate diagnostic or predictive biomarkers, respectively. The protein that demonstrated the largest differences between cases and controls was immunoglobulin E, with higher levels detected at baseline and across all time points in controls without CTRCD as compared with matched CTRCD cases (P<0.05). Similarly, in a validation study of 35 participants treated with doxorubicin and trastuzumab, high baseline immunoglobulin E levels were associated with a significantly lower risk of CTRCD (P=0.018). CONCLUSIONS:In patients receiving doxorubicin and trastuzumab, high baseline immunoglobulin E levels are associated with a lower risk of CTRCD. These novel findings suggest a new paradigm in cardio-oncology, implicating the immune system as a potential mediator of doxorubicin- and trastuzumab-induced cardiac dysfunction.
journal_name
Circ Resjournal_title
Circulation researchauthors
Beer LA,Kossenkov AV,Liu Q,Luning Prak E,Domchek S,Speicher DW,Ky Bdoi
10.1161/CIRCRESAHA.116.309004subject
Has Abstractpub_date
2016-10-28 00:00:00pages
1135-1144issue
10eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.116.309004journal_volume
119pub_type
杂志文章abstract::A period of prolonged vasodilation follows flow-restricted exercise of skeletal muscle. We tested the hypothesis that adenosine participates in mediating this vascular response. Vascularly isolated, anterior calf muscles of anesthetized dogs were stimulated to contract at a rate of 4 twitches/sec. Blood flow was held ...
journal_title:Circulation research
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doi:10.1161/CIRCRESAHA.114.302439
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doi:10.1161/01.RES.0000111803.92923.D6
更新日期:2004-02-20 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.68.5.1259
更新日期:1991-05-01 00:00:00
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doi:10.1161/CIRCRESAHA.120.317293
更新日期:2020-09-25 00:00:00
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journal_title:Circulation research
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更新日期:2001-06-08 00:00:00
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更新日期:1985-07-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.106.146399
更新日期:2007-07-06 00:00:00
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doi:10.1161/01.res.65.2.272
更新日期:1989-08-01 00:00:00
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doi:10.1161/01.res.36.6.761
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更新日期:2002-05-17 00:00:00
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doi:10.1161/01.res.72.4.827
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journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2000-11-10 00:00:00
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journal_title:Circulation research
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更新日期:2016-06-24 00:00:00