N 1,N12-Diacetylspermine as a Sensitive and Specific Novel Marker for Early- and Late-Stage Colorectal and Breast Cancers

Abstract

-diacetylspermine (DiAcSpm) in the urine of colorectal and breast cancer patients was examined to establish its usefulness as a novel diagnostic tool for detecting these cancers at clinically early stages. Experimental Design: Urine samples from 248 colon cancer patients and 83 breast cancer patients as well as 51patients with benign gastrointestinal diseases treated inTokyo Metropolitan Komagome Hospital during the period of August1999 toJanuary 2004 were collected. DiAcSpm was analyzed by ELISA and its sensitivity for malignant conditions was compared with that of serum carcinoembryonic antigen (CEA), CA19-9, and CA15-3. Results: The sensitivity of urinary DiAcSpm for colon cancer patients (n = 248) was 75.8% (mean F 2 SD for 52 healthy controls as a cutoff value), which was markedly higher than the sensitivities of serum CEA (39.5%, P < 0.0001) and CA19-9 (14.1%, P < 0.0001). DiAcSpm was elevated in 60% of tumor-node-metastasis cancer stage 0 + I patients, whereas only 10% (P < 0.0001) and 5% (P < 0.0001) of these patients were CEA-and CA19-9^positive, respectively.The sensitivity of urinary DiAcSpm for 83 cases of breast cancer (60.2%) was higher than the sensitivities of CEA (37.3%, P = 0.0032) and CA15-3 (37.3%, P = 0.0032). DiAcSpm was elevated in 28% of tumor-node-metastasis stage I + II patients, whereas only 3% (P = 0.0064) and 0% (P = 0.001) of these patients were CEA-and CA15-3^positive, respectively. Conclusion:The observations indicate that urinary DiAcSpm is a more sensitive marker than CEA, CA19-9, and CA15-3 and that it can efficiently detect colorectal and breast cancers at early stages.We reported previously that N 1 ,N 12 -diacetylspermine (DiAcSpm) is excreted in the urine of healthy persons, with small individual variations in the amount (1). We devised a high-performance liquid chromatography separation system connected to an in-line enzymatic detection system for DiAcSpm and carried out precise analyses of urinary DiAcSpm in healthy persons as well as patients with malignant diseases.Our analysis revealed that DiAcSpm may be useful as a novel diagnostic and prognostic tumor marker in that its excretion in urine is elevated significantly and frequently in patients with urogenital malignancies and tends to recover to the normal level on remission (2, 3). At the same time, we noted that monoacetylpolyamines that constitute a major part of urinary polyamines, including N-acetylputrescine, N 1 -acetylspermidine, and N 8 -acetylspermidine, were much less sensitive as markers for these urogenital malignancies than DiAcSpm and could not be considered practical tumor markers. The part of our observations concerning conventional monoacetylpolyamines was very well in accord with the popular evaluation of urinary polyamines at that time (4), but our results on DiAcSpm analysis were radically different from those on other polyamine derivatives and looked highly promising (2, 3).Although the biochemistry and clinical chemistry of DiAcSpm remain largely obscure at present because of the lack of intensiv...

Urinary Polyamines as Biomarkers for Ovarian Cancer

“…6,11Y13 In breast cancer, even earlystage disease seems to be associated with elevated levels of DiAcSpm in the urine. 13 In colon cancer, urinary DiAcSpm may be a better tumor marker than carcinoembryonic antigen or cancer antigen 19-9. 13,14 Besides being predictive markers, there is a possibility that DiAcSpm and DiAcSpd could be used also as prognostic markers, at least in testicular or prostatic cancer.…”

Breast Cancer Recurrence Risk Assessment: Is Non-Invasive Monitoring an Option?

“…Hiramatsu et al [90] studied N 1 N 12 -diacetylspermine as a potential urinary biomarker in breast cancer. This protein deriving from the polyamine metabolism in association with cell proliferation was significantly up-regulated in 80.3% of urines examined in 51 women with late-stage and metastasized breast cancer as compared to a healthy control cohort ( n = 51).…”

“…Interestingly, the same group of patients was simultaneously tested for their serum CA 15–3 and CEA levels. Even though these proteins have been suggested as potential monitoring biomarkers in the past, they accounted for a lower sensitivity of 60.8 and 58.8%, respectively [89, 90]. Beretov et al [91] chose a liquid chromatography with tandem-mass spectrometry approach to discover novel urinary protein biomarker candidates for breast cancer metastasis.…”

Do biofilms confer a pro-carcinogenic state?

“…An untargeted global metabolomics analysis revealed that an elevated N(1), N (12)-diacetylspermine pool, a polyamine relevant to oncogenesis, was in part due to contribution(s) from the bacterial biofilms. While excess levels of various polyamines have been recognized in association with colon cancer, including one study in which N(1), N (12)-diacetylspermine was detected in the urine of CRC patients, 5 this is the first direct link of this polyamine metabolite to the microbiome and, specifically, biofilm formation. A decreasing gradient from the proximal to distal colon in both healthy and disease states has been reported for polyamine levels and ornithine decarboxylase (ODC) prior to our study.…”