Evaluating the utility of N1,N12-diacetylspermine and N1,N8-diacetylspermidine in urine as tumor markers for breast and colorectal cancers

Umemori, Yoshifumi; Ohe, Yui; Kuribayashi, Kageaki; Tsuji, Naoki; Nishidate, Toshihiko; Kameshima, Hidekazu; Hirata, Koichi; Watanabe, Naoki

doi:10.1016/j.cca.2010.07.018

Cited by 45 publications

(31 citation statements)

References 18 publications

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“…There are two papers on spermines 27, 28. Umemori and co-workers examined N1,N12diacetylspermine (DiAcSpm) and N1, N8 diacetylspermidine (DiAcSpd) in various groups of subjects (table 1) and found that both were significantly higher in cancer patients than in HC (respectively p=0.01 and p<0.01).…”

Section: Resultsmentioning

confidence: 99%

“…Among natural polyamines, the concentrations of diacetylated spermine and spermidine increase in urine from cancer patients 101-103. Urinary DiAcSpm and DiAcSpd have been evaluated in BC and CRC patients in two studies 27, 28. In Hiramatsu's study 28, urinary DiAcSpm was found to have a markedly higher SE (75.8%) compared with serum CEA (39.5%) and CA19-9 (14.1%) in CRC patients 26; in Umemori's study 27, the SE of DiAcSpm and DiAcSpd in CRC patients was respectively 69.6% and 36.3%.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have compared the values obtained with urinary and serum markers 23 and others have compared these with the FOBT 24, thus increasing their diffusion and the interest in developing laboratory techniques capable of detecting specific molecules. Several markers have been vetted, including nucleosides 25, the methylation level of specific genes 23,24, species deriving from oxidative stress 26, spermine concentration 27-29, and enzyme activities 30,31. In the past decade, urinary prostaglandins (PG) have been examined as possible early markers of high-risk adenoma (HRA) 32-35and adenocarcinoma 35, 36.…”

Section: Introductionmentioning

confidence: 99%

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Role of Urinary Biomarkers in the Diagnosis of Adenoma and Colorectal Cancer: A Systematic Review and Meta-Analysis

Altobelli¹,

Angeletti²,

Latella³

2016

J. Cancer

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The growing interest in enhancing and spreading colorectal cancer (CRC) screening has been stimulating the exploration of novel biomarkers with greater sensitivity and specificity than immunochemical faecal occult blood test (iFOBT). The present study provides i) a systematic review of the urinary biomarkers that have been tested to achieve early CRC diagnosis and assess the risk of colorectal adenoma and adenocarcinoma, and ii) a meta-analysis of the data regarding the urinary prostaglandin (PG) metabolite PGE-M.As regard to gene markers, we found significantly different percent methylation of the vimentin gene in CRC patients and healthy controls (HC) (p<0.0001). Respect to metabolism of nitrogenous bases, cytidine, 1-methyladenosine, and adenosine, have higher concentrations in CRC patients than in HC (respectively, p<0.01, p=0.01, and p<0.01). As regard to spermine we found that N1,N12 diacetyl spermine (DiAcSpm) and N1, N8 diacetylspermidine (DiAcSpd) were significantly higher in CRC than in HC (respectively p=0.01 and p<0.01). Respect to PGE-M, levels were higher in CRC than in those with multiple polyposis (p<0.006) and HC subjects (p<0.0004). PGE-M seems to be the most interesting and promising urinary marker for CRC and adenoma risk assessment and for CRC screening.In conclusion, evidence suggests that urinary biomarker could have a potential role as urinary biomarkers in the diagnosis of colorectal cancer. Particularly, PGE-M seems to be the most promising urinary marker for CRC early detection.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of Urinary Biomarkers in the Diagnosis of Adenoma and Colorectal Cancer: A Systematic Review and Meta-Analysis

Altobelli¹,

Angeletti²,

Latella³

2016

J. Cancer

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“…According to this study, colonic bacteria utilize polyamines to build biofilms (producing DAS), and this biofilm formation induces pro-inflammatory and pro-carcinogenic effects in the host tissues, increasing the risk of tumour formation. Interestingly, some metabolomic studies have associated DAS with other cancers, including cancers of the lung 72 , breast 73 , blood 74 and bladder 75 , as well as identifying it as a dietary metabolite 76 . Thus, further studies assessing the roles of diet and bacteria in cancers are of the utmost importance.…”

Section: Novel Biological Insightsmentioning

confidence: 99%

Metabolomics: beyond biomarkers and towards mechanisms

Johnson

Ivanišević

Siuzdak

2016

Nat Rev Mol Cell Biol

2,023

1,362

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Metabolomics, which is the profiling of metabolites in biofluids, cells and tissues, is routinely applied as a tool for biomarker discovery. Owing to innovative developments in informatics and analytical technologies, and the integration of orthogonal biological approaches, it is now possible to expand metabolomic analyses to understand the systems-level effects of metabolites. Moreover, because of the inherent sensitivity of metabolomics, subtle alterations in biological pathways can be detected to provide insight into the mechanisms that underlie various physiological conditions and aberrant processes, including diseases.

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“…Takahashi et al found that urinary DAS was an prognostic marker for NSCLC (hazard ratio of 4.652 [95% CI, 2.092-10.35]), particularly in squamous cell carcinoma [10]. Additionally, urinary DAS and N1,N8-diacetylspermidine have shown promise as diagnostic markers for breast and colorectal cancers [14].…”

Section: Commentarymentioning

confidence: 99%

N1,N12-Diacetylspermine as a Blood Based Lung Cancer Biomarker

Fahrmann¹,

Hanash²

2016

Biochem Anal Biochem

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It is becoming well recognized that metabolic perturbations are inherent hallmarks of tumorigenesis [1,2]. Metabolites represent the functional products of cellular processes, which are highly responsive to both pathological and environmental stimuli. As such, metabolites are the closest representation of an individual's current physiological state. Therefore, exploration of metabolic alterations in the context of disease pathophysiology, most notably cancer, holds great promise and considerable clinical value. This field of research has benefited from technological advances in mass spectrometry and ultraviolet-visible spectroscopic analyses that have enabled comprehensive metabolomic analyses of diverse arrays of metabolites, polyphenols and lipids in a variety of biological matrices with substantial robustness and sensitivity [3][4][5][6][7][8][9]. As a result, interest in the application of metabolomics to identify key metabolic differences related to pathological conditions has expanded. Indeed, metabolomics has been explored to gain insights into the pathophysiology of cancer, develop methods predictive of disease onset, and reveal new biomarkers relevant to disease diagnosis and prognosis [4-6] [10-12].The application of metabolomics to the discovery of blood-based biomarker in cancer has substantial potential clinical relevance. Recently, we have identified the polyamine end-product N1, N12-diacetylspermine (DAS) as a novel pre-diagnostic serum biomarker for non-small cell lung cancer (NSCLC) [6]. In this study, DAS alone yielded an AUC of 0.610 and AUC 0.710 for sera collected 6 to 12 months and 0 to 6 months before onset of symptoms and diagnosis, respectively, in the discovery set. These findings were subsequently confirmed in an independent and blinded validation set [6]. Single markers are unlikely to exhibit sufficient performance to be fully informative of disease status. Therefore in our study we examined the performance of DAS in combination with another marker Pro-SFTPB, which we previously validated as a blood based marker for NSCLC [13]. The combination of DAS and Pro-SFTPB resulted in improved performance compared to either alone (Overall AUCs of 0.732, 0.650 and 0.699 in the validation set for Pro-SFTPB + DAS, DAS only and Pro-SFTPB only, respectively) [6]. This study highlights the potential contributions of metabolomics to the discovery of biomarkers that inform about disease risk before the onset of symptoms and, importantly, illustrates the value of DAS as a complementary non-invasive biomarker. While the latter findings implicate that DAS is not specific to lung cancer, it does highlight conserved metabolic dysregulation of polyamine biosynthesis, which is strongly associated with tumorigenesis [15,16]. However, one caveat that must always be considered is whether serum or urinary DAS differs between malignant and benign tumors. This is particularly relevant in lung cancer as screening methodologies have been largely hindered by high false positive rates, a consequence of the low preval...

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Evaluating the utility of N1,N12-diacetylspermine and N1,N8-diacetylspermidine in urine as tumor markers for breast and colorectal cancers

Cited by 45 publications

References 18 publications

Role of Urinary Biomarkers in the Diagnosis of Adenoma and Colorectal Cancer: A Systematic Review and Meta-Analysis

Role of Urinary Biomarkers in the Diagnosis of Adenoma and Colorectal Cancer: A Systematic Review and Meta-Analysis

Metabolomics: beyond biomarkers and towards mechanisms

N1,N12-Diacetylspermine as a Blood Based Lung Cancer Biomarker

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