Urinary Polyamines as Biomarkers for Ovarian Cancer

Abstract

ObjectivesElevated concentrations of polyamines have been found in urine of patients with malignant tumors, including ovarian cancer. Previous research has suffered from poorly standardized detection methods. Our liquid chromatography–tandem mass spectrometry (LC-MS/MS) method is capable of simultaneous standardized analysis of most known polyamines. Liquid chromatography–tandem mass spectrometry has not previously been used in the differential diagnostics of ovarian tumors in postmenopausal women.Materials and MethodsIn this prospective study, postmenopausal women (n = 71) presenting with an adnexal mass and, as controls, women with genital prolapse or urinary incontinence scheduled for surgery (n = 22) were recruited in the study. For analysis of the polyamines, a morning urine sample was obtained before surgery. Preoperative serum CA125 concentrations were determined in the study group.ResultsTwenty-three women with benign and 37 with malignant ovarian tumors were eligible. Of all analyzed polyamines, only urinary N1,N12-diacetylspermine showed statistically significant differences between all groups except controls versus benign tumors. N1,N12-diacetylspermine was elevated in malignant versus benign tumors (P < 0.001), in high-grade versus low malignant potential tumors (P < 0.001), in stage III to IV versus stage I to II cancers (P < 0.001), and even in early-stage cancer (stage I–II) versus benign tumors (P = 0.017). N1,N12-diacetylspermine had better sensitivity (86.5%) but lower specificity (65.2%) for distinguishing benign and malignant ovarian tumors than CA125 with a cut-off value of 35 kU/L (sensitivity, 75.7%; specificity, 69.6%).ConclusionsUrinary N1,N12-diacetylspermine seems to be able to distinguish benign and malignant ovarian tumors as well as early and advanced stage, and low malignant potential and high-grade ovarian cancers from each other, respectively.

The Translational Status of Cancer Liquid Biopsies

“…Furthermore, urine and plasma polyamine content in cancer patients can mirror intracellular levels of these metabolites, presenting an opportunity to use them as liquid biopsy biomarkers. The biomarker potential of polyamines was recently investigated using targeted analysis with LC MS/MS in colorectal [347,348], ovarian [349], and prostate cancer [350].…”

Elevated Polyamines in Saliva of Pancreatic Cancer

“…We previously observed the change of metabolite concentration in salivary samples collected from PC patients [20]. Among metabolites, polyamines in non-invasively available biofluids have been reported as possible biomarkers of various cancers [21][22][23]. Elevation of urinary polyamines and the positive correlation between their concentrations in PC tissue is well known [24].…”

Upregulation of Polyamine Transport in Human Colorectal Cancer Cells

“…Cancer patients exhibit elevated concentrations of polyamines in body fluids, especially in their acetylated form [7][8][9]. This relationship between cancer and polyamines has opened the door for polyamines as cancer biomarkers but more likely as markers of response rather than of diagnosis [10]. Cancer cells also have upregulated ornithine decarboxylase (ODC) [11], which confers a higher capacity for polyamine synthesis to cope with the demand for continuous proliferation.…”