1. A MYC-Driven Plasma Polyamine Signature for Early Detection of Ovarian Cancer
- Author
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Kim Anh Do, Eunice Murage, R. R. Wu, Samir M. Hanash, James P. Long, Makoto Kobayashi, Zhen Lu, Ehsan Irajizad, Johannes F. Fahrmann, Jody Vykoukal, Jennifer B. Dennison, Joseph Celestino, Robert C. Bast, and Karen H. Lu
- Subjects
0301 basic medicine ,Cancer Research ,endocrine system diseases ,polyamines ,lcsh:RC254-282 ,Article ,Pathogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,McNemar's test ,Medicine ,early detection ,Receiver operating characteristic ,business.industry ,Area under the curve ,blood-based biomarkers ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,female genital diseases and pregnancy complications ,Exact test ,030104 developmental biology ,ovarian cancer ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,Polyamine ,business ,Ovarian cancer - Abstract
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.
- Published
- 2021