The clinical usefulness of urinary N1,N12-diacetylspermine (DiAcSpm) levels as a tumor marker in patients with colorectal cancer

Nakayama, Yoshifumi; Torigoe, Takayuki; Minagawa, Nozomi; Yamaguchi, Koji

doi:10.3892/ol.2012.625

Cited by 14 publications

(8 citation statements)

References 15 publications

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“…Rapidly growing cells, such as cancer cells, generally have increased intracellular polyamine levels and actively metabolize polyamines. An elevated N 1 , N 12 -diacetylspermine level may indicate rapid proliferation of cancer cells themselves 32 , and has been reported as a more sensitive biomarker than CEA, CA19-9 or CA15-3 for CRC diagnosis at early stages 30 , 31 , 32 , 33 .…”

Section: Discussionmentioning

confidence: 99%

Profiling of polar urine metabolite extracts from Chinese colorectal cancer patients to screen for potential diagnostic and adverse-effect biomarkers

Deng¹,

Yao²,

Chen³

et al. 2020

J. Cancer

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Background: Metabolomics has demonstrated its potential in the early diagnosis, drug safety evaluation and personalized toxicology research of various cancers. Objectives: We aim to screen for potential diagnostic and capecitabine-related adverse effect (CRAE) biomarkers from urinary endogenous metabolites in Chinese colorectal cancer (CRC) patients. Methods: The metabolic profiles of 139 CRC patients and 50 non-neoplastic controls were analyzed using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry. Results: There were 41 metabolites identified between the CRC patients and the non-neoplastic controls, and 19 metabolites were identified between CRC patients with and without CRAE. Based on these identified metabolites, bioinformatic analysis and prediction model construction were completed. Most of these differential metabolites have important roles in cell proliferation and differentiation and the immune system. Based on binary logistic regression, a CRC prediction model, composed of 3-methylhistidine, N-heptanoylglycine, N 1 ,N 12 -diacetylspermine and hippurate, was established, with an area under curve (AUC) of 0.980 (95% CI: 0.953-1.000; sensitivity: 94.3%; specificity: 92.0%) in the training set, and an AUC of 0.968 (95% CI: 0.933-1.000; sensitivity: 89.9%; specificity: 92.0%) in the testing set. In addition, methionine and 4-pyridoxic acid can be combined to predict hand foot syndrome, with an AUC of 0.884; ubiquinone-1 and 4-pyridoxic acid can be combined to predict anemia, with an AUC of 0.889; and 5-acetamidovalerate and 3,4-methylenesebacic acid can be combined to predict neutropenia, with an AUC of 0.882. Conclusion: The profiling of urine polar metabolites has great potential in the early detection of CRC and the prediction of CRAE.

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Section: Discussionmentioning

confidence: 99%

Profiling of polar urine metabolite extracts from Chinese colorectal cancer patients to screen for potential diagnostic and adverse-effect biomarkers

Deng¹,

Yao²,

Chen³

et al. 2020

J. Cancer

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“…CRC is one of the leading causes of cancer deaths in the world, and diagnosis at an early onset followed by surgical intervention is currently the best way to cure the disease and decrease mortality. It is therefore important to develop detection markers to detect asymptomatic CRCs at earlier stages, while the sensitivities of CEA and CA19‐9 were reported to be relatively low in early‐stage CRCs . Our previous studies of DNA methylation in CRC and precancerous lesions revealed that accumulation of aberrant DNA methylation was mostly completed by the adenoma stage , suggesting the possible usefulness of assessing aberrant methylation in plasma DNA in detecting early‐stage CRCs.…”

Section: Discussionmentioning

confidence: 99%

“…The fecal occult blood test, however, has a low specificity, ranging from 0.3% to 0.5% . CEA and CA19‐9 are not frequently positive in CRC at early stages (I and II), and their sensitivities are <50% . These methods are not satisfactory for early cancer detection, and a new, noninvasive technique to detect early‐stage malignancies with higher sensitivity than these protein markers would be useful as a first screening test, before the need of invasive examinations, for example, barium enemas and colonoscopies .…”

Section: Introductionmentioning

confidence: 99%

Aberrant promoter methylation of PPP1R3C and EFHD1 in plasma of colorectal cancer patients

et al. 2014

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Aberrant DNA methylation is a common epigenetic alteration involved in colorectal cancer (CRC). In our previous study, we performed methylated DNA immunoprecipitation-on-chip analysis combined with gene re-expression analysis by 5-aza-2′-deoxycytidine treatment, to identify methylation genes in CRC genome widely. Among these genes, 12 genes showed aberrant hypermethylation frequently in >75% of 149 CRC samples but did not in normal samples. In this study, we aim to find out any of these methylation genes to be utilized for CRC detection using plasma DNA samples. Primers for methylation-specific PCR and pyrosequencing were designed for seven of the 12 genes. Among them, PPP1R3C and EFHD1 were rarely hypermethylated in peripheral blood cells, but frequently hypermethylated in 24 CRC tissue samples and their corresponding plasma samples. In plasma samples, PPP1R3C was methylated in 81% (97/120) of CRC patients, but only in 19% (18/96) of noncancer patients (P = 6 × 10−20, Fisher's exact test). In combined analysis with EFHD1, both genes were methylated in 53% (64/120) of CRC patients, but only in 4% (4/96) of noncancer patients (P = 2 × 10−16), giving high specificity of 96%. At least one of the two genes was methylated in 90% (108/120) of CRC patients, and 36% (35/96) of control patients, giving high sensitivity of 90%. Compared with low sensitivity of carcinoembryonic antigen (17% at stage I, 40% at stage II) and CA19-9 (0% at stage I, 13% at stage II) for early-stage CRCs, sensitivity of aberrant methylation was significantly higher: PPP1R3C methylation at 92% (11/12) for stage I and 77% (23/30) for stage II, and methylation of at least one gene at 100% (12/12) for stage I and 87% (26/30) for stage II. PPP1R3C methylation or its combined use of EFHD1 methylation was highly positive in CRC plasma samples, and they might be useful in detection of CRC, especially for early-stage CRCs.

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“…Increased levels of acetylated polyamines (APs) in urine have long been associated with cancer [1]. Specifically, N 1 ,N 12 -diacetylspermine (DAS), N 1 -acetylspermine (ASP), and N 8acetylspermidine (ASD) have been found to be elevated in urine of patients with a wide range of cancer types [2][3][4][5][6][7][8]. In recent years APs have been found to be elevated in matrices other than urine [9].…”

Section: Introductionmentioning

confidence: 99%

Rapid LC-MS/MS quantification of cancer related acetylated polyamines in human biofluids

DeFelice

Fiehn

2019

Talanta

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Increased urinary acetylated polyamines (APs) are reported as cancer biomarkers in many studies. N 1 ,N 12-diacetylspermine has been proposed as a biomarker indicative of different cancers in urine and plasma. N 1-Acetylspermine has previously been found to be increased in the saliva of patients with breast cancer; however, in plasma this metabolite was too low abundant to be detected by previous analytical methods. In addition, no method has been reported to perform AP analysis on the level of speed, robustness and sensitivity required for daily clinical routines. Here we describe a high-throughput sample preparation and LC-MS/MS method for the fast, accurate and precise quantification of three APs: N 8-acetylspermidine, N 1-acetylspermine, and N 1 ,N 12-diacetylspermine in plasma, urine and saliva. Stable isotope labeled N 1 ,N 12diacetylspermine was used as internal standard. Robustness was validated by intra-and inter-day reproducibility. Precision and accuracy of the method were tested at six concentration levels from 0.0375 to 750 ng/mL resulting in less than 15% relative standard deviation and less than 15% percent error in quantification. Using 96-well plates, the assay described herein allows for preparing, analyzing, and quantifying 240 samples per day for a single researcher to quantify three APs commonly related to cancer status.

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The clinical usefulness of urinary N1,N12-diacetylspermine (DiAcSpm) levels as a tumor marker in patients with colorectal cancer

Cited by 14 publications

References 15 publications

Profiling of polar urine metabolite extracts from Chinese colorectal cancer patients to screen for potential diagnostic and adverse-effect biomarkers

Profiling of polar urine metabolite extracts from Chinese colorectal cancer patients to screen for potential diagnostic and adverse-effect biomarkers

Aberrant promoter methylation of PPP1R3C and EFHD1 in plasma of colorectal cancer patients

Rapid LC-MS/MS quantification of cancer related acetylated polyamines in human biofluids

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