A MYC-Driven Plasma Polyamine Signature for Early Detection of Ovarian Cancer

MYC is an oncogenic driver in the pathogenesis of ovarian cancer. We previously demonstrated that MYC regulates polyamine metabolism in triple-negative breast cancer (TNBC) and that a plasma polyamine signature is associated with TNBC development and progression. We hypothesized that a similar plasm...

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Bibliographic Details
Published in:Cancers 2021-02, Vol.13 (4), p.913
Main Authors: Fahrmann, Johannes F, Irajizad, Ehsan, Kobayashi, Makoto, Vykoukal, Jody, Dennison, Jennifer B, Murage, Eunice, Wu, Ranran, Long, James P, Do, Kim-Anh, Celestino, Joseph, Lu, Karen H, Lu, Zhen, Bast, Robert C, Hanash, Samir
Format: Article
Language:English
Subjects:
Biomarkers
Breast cancer
Classification
Complementarity
Mass spectrometry
Mass spectroscopy
Medical screening
Myc protein
Ovarian cancer
Plasma
Polyamines
Scientific imaging
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Summary:MYC is an oncogenic driver in the pathogenesis of ovarian cancer. We previously demonstrated that MYC regulates polyamine metabolism in triple-negative breast cancer (TNBC) and that a plasma polyamine signature is associated with TNBC development and progression. We hypothesized that a similar plasma polyamine signature may associate with ovarian cancer (OvCa) development. Using mass spectrometry, four polyamines were quantified in plasma from 116 OvCa cases and 143 controls (71 healthy controls + 72 subjects with benign pelvic masses) (Test Set). Findings were validated in an independent plasma set from 61 early-stage OvCa cases and 71 healthy controls (Validation Set). Complementarity of polyamines with CA125 was also evaluated. Receiver operating characteristic area under the curve (AUC) of individual polyamines for distinguishing cases from healthy controls ranged from 0.74-0.88. A polyamine signature consisting of diacetylspermine + N-(3-acetamidopropyl)pyrrolidin-2-one in combination with CA125 developed in the Test Set yielded improvement in sensitivity at >99% specificity relative to CA125 alone (73.7% vs 62.2%; McNemar exact test 2-sided P: 0.019) in the validation set and captured 30.4% of cases that were missed with CA125 alone. Our findings reveal a MYC-driven plasma polyamine signature associated with OvCa that complemented CA125 in detecting early-stage ovarian cancer.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13040913