Zheng HZ, Wang P, Zheng HJ, Wang ZQ, Li QX, Chen HW, Chen HQ, Lei QC. Urinary N1, N12-diacetylspermine as a potential tumor biomarker for gastric and colorectal cancer. World J Gastroenterol 2026; 32(33): 118185 [DOI: 10.3748/wjg.118185]
Corresponding Author of This Article
Qiu-Cheng Lei, MM, Attending Physician, Department of Hepatobiliary and Pancreatic Surgery, The First People’s Hospital of Foshan (Foshan Hospital Affiliated to Southern University of Science and Technology), School of Medicine, Southern University of Science and Technology, No. 81 Lingnan Avenue North, Foshan 528000, Guangdong Province, China. lqiuchenggd@163.com
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Oncology
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Zheng HZ, Wang P, Zheng HJ, Wang ZQ, Li QX, Chen HW, Chen HQ, Lei QC. Urinary N1, N12-diacetylspermine as a potential tumor biomarker for gastric and colorectal cancer. World J Gastroenterol 2026; 32(33): 118185 [DOI: 10.3748/wjg.118185]
Hua-Zhen Zheng, Hui-Jie Zheng, Zi-Qi Wang, Qi-Xin Li, Huo-Qiang Chen, Department of Laboratory Medicine, The First People’s Hospital of Foshan (Foshan Hospital Affiliated to Southern University of Science and Technology), School of Medicine, Southern University of Science and Technology, Foshan 528000, Guangdong Province, China
Peng Wang, Department of Gastrointestinal Surgery, The First People’s Hospital of Foshan (Foshan Hospital Affiliated to Southern University of Science and Technology), School of Medicine, Southern University of Science and Technology, Foshan 528000, Guangdong Province, China
Huan-Wei Chen, Qiu-Cheng Lei, Department of Hepatobiliary and Pancreatic Surgery, The First People’s Hospital of Foshan (Foshan Hospital Affiliated to Southern University of Science and Technology), School of Medicine, Southern University of Science and Technology, Foshan 528000, Guangdong Province, China
Co-corresponding authors: Huo-Qiang Chen and Qiu-Cheng Lei.
Author contributions: Zheng HZ and Wang P contributed equally to data collection, statistical analysis, and original draft preparation, they contributed equally to this article and are the co-first authors of this manuscript; Zheng HZ, Wang ZQ, and Zheng HJ performed sample testing; Li QX and Chen HW conducted participant recruitment; Zheng HZ, Wang P, and Lei QC acquired funding and oversaw all stages of the project; Zheng HZ, Wang P, Zheng HJ, and Wang ZQ contributed to patient follow-up; Chen HQ and Lei QC jointly supervised experimental design, writing, review, and editing, they are the co-corresponding authors of this manuscript; and all authors thoroughly reviewed and endorsed the final manuscript.
Supported by National Natural Science Foundation of China (General Program), No. 82400651; and the Foshan Science and Technology Innovation Project, No. 2320001006781.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Foshan First People’s Hospital, approval No. Medical ethics 2016 No. 3.
Informed consent statement: All participants provided written informed consent for both participation in the study and publication of the data.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The raw data that support the findings of this study are available from the corresponding author upon reasonable request.
Corresponding author: Qiu-Cheng Lei, MM, Attending Physician, Department of Hepatobiliary and Pancreatic Surgery, The First People’s Hospital of Foshan (Foshan Hospital Affiliated to Southern University of Science and Technology), School of Medicine, Southern University of Science and Technology, No. 81 Lingnan Avenue North, Foshan 528000, Guangdong Province, China. lqiuchenggd@163.com
Received: December 29, 2025 Revised: February 25, 2026 Accepted: April 10, 2026 Published online: September 7, 2026 Processing time: 227 Days and 18.3 Hours
Abstract
BACKGROUND
Previous studies have reported elevated urinary N1, N12-diacetylspermine (DiAcSpm) levels in various cancers. We therefore hypothesized that urinary DiAcSpm could serve as a potential biomarker for gastric and colorectal cancers (CRCs) and may also have prognostic value.
AIM
To assess the diagnostic potential of urinary DiAcSpm for gastric and CRC and to explore its prognostic significance.
METHODS
A total of 209 urine samples were collected from patients with gastrointestinal cancers, benign gastrointestinal diseases, and healthy controls. Pre- and post-treatment clinical data were obtained for all participants. Urinary DiAcSpm levels were measured using a commercially available reagent kit via an immunoturbidimetric assay on an automated biochemical analyzer.
RESULTS
Urinary DiAcSpm concentrations were significantly higher in patients with gastric and CRCs compared with benign disease patients and healthy controls. It discriminated gastric cancer (GC) from healthy controls with an area under the curve (AUC) of 0.714 [95% confidence interval (CI): 0.613-0.815], sensitivity of 59.65%, and specificity of 76.19%. For CRC, the AUC was 0.736 (95%CI: 0.648-0.824), with sensitivity of 42.11% and specificity of 95.24%. Combining DiAcSpm with carcinoembryonic antigen improved diagnostic performance [GC: AUC = 0.755 (95%CI: 0.657-0.852), sensitivity = 94.74%, specificity = 50.00%; CRC: AUC = 0.813 (95%CI: 0.739-0.887), sensitivity = 91.23%, specificity = 58.73%]. Urinary DiAcSpm levels significantly decreased after chemotherapy in CRC patients. High DiAcSpm levels were associated with distant metastasis in GC patients.
CONCLUSION
Urinary DiAcSpm levels are markedly elevated in patients with GC and CRC. While its standalone diagnostic accuracy requires further improvement, DiAcSpm shows promise as a complementary marker to existing serum biomarkers in combined diagnostic strategies.
Core Tip: Urinary N1, N12-diacetylspermine (DiAcSpm) was evaluated as a potential non-invasive biomarker for gastric and colorectal cancer. Levels were significantly elevated in cancer patients and showed moderate diagnostic value, which improved when combined with carcinoembryonic antigen. Urinary DiAcSpm levels decreased after chemotherapy in colorectal cancer patients, and high levels correlated with distant metastasis in gastric cancer patients. These findings support the potential of urinary DiAcSpm, though prospective studies in larger cohorts are warranted to confirm its clinical utility.
Citation: Zheng HZ, Wang P, Zheng HJ, Wang ZQ, Li QX, Chen HW, Chen HQ, Lei QC. Urinary N1, N12-diacetylspermine as a potential tumor biomarker for gastric and colorectal cancer. World J Gastroenterol 2026; 32(33): 118185
Gastric cancer (GC) and colorectal cancer (CRC) are among the most prevalent gastrointestinal malignancies worldwide. In 2022, over 968000 new GC cases were reported, resulting in 660000 deaths[1]. Although GC incidence has declined, it remains the fifth highest in both incidence and mortality[1]. CRC ranks third in incidence and second in mortality, with over 1.9 million new cases and 904000 deaths reported in 2022[1]. Early diagnosis and intervention are essential to prevent disease progression and improve patient outcomes[2,3]. Current early detection relies on endoscopy, which requires specialized equipment and experienced clinicians. However, endoscopy is invasive and carries risks such as bleeding or perforation, often leading to poor patient compliance. These limitations make endoscopic screening unsuitable for large-scale populations, particularly in resource-limited settings[3,4]. Therefore, identifying noninvasive, sensitive, and specific biomarkers for early GC and CRC detection is a critical research priority.
N1, N12-diacetylspermine (DiAcSpm) is a minor human polyamine, constituting approximately 0.46% of total urinary polyamines in healthy individuals[5]. Polyamines play essential roles in cellular proliferation, gene expression, membrane stability, and apoptosis[6]. Polyamine levels have been reported to increase during malignant transformation. Previous studies showed that peritoneal macrophages from tumor-bearing mice can produce DiAcSpm[7], and DiAcSpm expression is elevated in CRC, liver metastases, and breast tumors of varying grades[8-10]. Direct evidence of DiAcSpm production by human cancer cells in vivo remains limited. However, increased urinary polyamine excretion in prostate cancer patients, compared to healthy controls, was first observed by Professor Sanford in the mid-1970s[11]. Hiramatsu et al[12] in 1995 highlighted the potential of DiAcSpm as a tumor marker. Subsequent studies have reported elevated urinary DiAcSpm in multiple cancers, including breast[13-15], lung[16], colorectal[13,17,18], ovarian[19], lymphoma[20], hepatocellular carcinoma[19,21], and pancreatic cancer[22]. Despite these associations, the precise mechanisms linking DiAcSpm to cancer progression remain poorly understood.
Given the value of noninvasive urinary biomarkers for cancer diagnosis and monitoring, this study aimed to evaluate urinary DiAcSpm as a diagnostic and prognostic biomarker for GC and CRC in a Chinese population.
MATERIALS AND METHODS
Patients and ethical considerations
A total of 241 participants undergoing pathological evaluation for digestive tract disorders - including GC, CRC, and benign gastrointestinal diseases (BGD) - were prospectively recruited at the First People’s Hospital of Foshan from August 2017 to July 2018. Thirty-two participants were excluded due to incomplete data or failure to meet inclusion criteria, leaving 209 participants for analysis. Patients had no history of pregnancy or secondary malignancies and had not received prior chemotherapy, radiotherapy, or immunotherapy. All participants were over 18 years old and had not taken hormones or estrogenic medications within 14 days prior to urine collection. This study was approved by the Ethics Board of Foshan First People’s Hospital, approval No. Medical Ethics 2016 No. 3 and conducted in accordance with the Helsinki Declaration. Written informed consent was obtained from all participants. Study design is illustrated in Figure 1.
Midstream urine samples were collected at any time of day, either used immediately or stored at -20 °C until analysis. Urinary DiAcSpm concentrations were determined using the Diacetylspermine Test Kit (Immunoturbidimetry) (Maidi Bio-Tech Co., Liaoning Province, China) following the manufacturer’s protocol. Briefly, urine samples were centrifuged at 3000 rpm for 10 minutes at room temperature. The supernatant was collected, and reagents were added sequentially as instructed. DiAcSpm standards were used to construct a standard curve, and sample concentrations were calculated using the ADVIA 2400 Chemistry System (Siemens Ltd., China). DiAcSpm values were normalized to urinary creatinine (Cre) using the formula: Corrected DiAcSpm = DiAcSpm (nM)/Cre (μmol/L)/0.1131. Results are expressed as μmol/g· Cre.
Collect clinical data and measurement of CEA and CA199
The following information was obtained from patients’ medical records or through interviews: Age, sex, cancer type, disease stage, treatment, and therapeutic response. Serum carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) concentrations were measured using a Cobas E602 electrochemiluminescence immunoassay analyzer (Hoffmann-La Roche Inc., Switzerland) according to the manufacturer’s instructions.
Statistical analysis
All statistical analyses were performed using R version 4.2.1 and SPSS software (SPSS 27.0, IBM, United States). Continuous variables that did not follow a normal distribution were described using the median and interquartile range. The Kruskal-Wallis test was used to compare DiAcSpm, CEA, and CA199 levels among GC, BGD, and healthy controls. Receiver operating characteristic curves were plotted, and the area under the curve (AUC) with corresponding 95% confidence intervals (CI) was calculated to evaluate diagnostic performance. The correlation between serum CEA and urinary DiAcSpm was assessed using Spearman’s correlation analysis. Patients were categorized into high- and low-level groups based on the median urinary DiAcSpm concentration. Associations with clinical features were analyzed using the χ2 test. Statistical significance was defined as a two-tailed P value < 0.05.
RESULTS
Patients and controls
A total of 105 patients with pathologically confirmed diagnoses (42 GC and 63 CRC) and 104 controls (57 BGD and 47 healthy individuals) were included. Among the 57 BGD patients, 39 had gastritis and 18 had gastric/intestinal polyps, with urinary DiAcSpm concentrations of 0.63 (0.43-0.86) μmol/g· Cre and 0.49 (0.42-0.77) μmol/g· Cre, respectively, showing no significant difference between the groups (P = 0.6004). Serum CEA and CA199 levels in GC patients were significantly higher than those in BGD patients and healthy controls (all P < 0.05). Similarly, CRC patients exhibited markedly elevated serum CEA and CA199 levels compared to BGD patients and healthy controls (all P < 0.05) (Table 1).
Table 1 Clinical characteristics of the study participants.
Elevated urinary DiAcSpm concentrations in GC and CRC patients
Urinary DiAcSpm concentrations in GC patients were significantly higher than those in BGD patients [0.82 (0.61-1.25) μmol/g· Cre vs 0.56 (0.41-0.85) μmol/g· Cre, P = 0.0085] and healthy controls [0.82 (0.61-1.25) μmol/g· Cre vs 0.58 (0.47-0.79) μmol/g· Cre, P = 0.0301] (Table 1 and Figure 2A). CRC patients also exhibited higher urinary DiAcSpm concentrations compared to BGD [0.83 (0.56-1.35) μmol/g· Cre vs 0.56 (0.41-0.85) μmol/g· Cre, P = 0.0004] and healthy controls [0.83 (0.56-1.35) μmol/g· Cre vs 0.58 (0.47-0.79) μmol/g· Cre, P = 0.0026] (Table 1 and Figure 2B). No significant difference in urinary DiAcSpm concentrations was observed between BGD patients and healthy controls (all P > 0.05) (Figure 2).
Figure 2 The levels of urinary N1, N12-diacetylspermine concentrations.
A: Gastric cancer patients vs healthy controls and patients with benign gastrointestinal diseases; B: Colorectal cancer patients vs healthy controls and patients with benign gastrointestinal diseases. aP < 0.05, bP < 0.01, cP < 0.001. BGD: Benign gastrointestinal diseases; GC: Gastric cancer; CRC: Colorectal cancer.
Diagnostic performance of urinary DiAcSpm as an individual biomarker for GC and CRC
Urinary DiAcSpm demonstrated moderate diagnostic accuracy for distinguishing GC from healthy controls (AUCDiAcSpm = 0.714, 95%CI: 0.613-0.815; Figure 3A). For CRC, urinary DiAcSpm and serum CEA showed comparable diagnostic performance (AUC DiAcSpm = 0.736, 95%CI: 0.648-0.824; AUCCEA = 0.794, 95%CI: 0.715-0.873; Figure 3B). DiAcSpm exhibited superior diagnostic ability compared to CA199 (for GC: AUCCA199 = 0.581, 95%CI: 0.465-0.697; for CRC: AUCCA199 = 0.585, 95%CI: 0.481-0.688; Figure 3A and B). The optimal cutoff for urinary DiAcSpm to distinguish GC from healthy controls was 0.63 μmol/g· Cre (sensitivity 59.65%, specificity 76.19%), and for CRC it was 0.475 μmol/g· Cre (sensitivity 42.11%, specificity 95.24%).
Figure 3 Diagnostic values of urinary N1, N12-diacetylspermine, serum carcinoembryonic antigen, and carbohydrate antigen 199 for gastric cancer and colorectal cancer, and their correlation.
A: Receiver operating characteristic curves of urinary N1, N12-diacetylspermine (DiAcSpm), serum carcinoembryonic antigen (CEA) and carbohydrate antigen 199 for gastric cancer patients; B: Receiver operating characteristic curves of urinary DiAcSpm, serum CEA and carbohydrate antigen 199 for colorectal cancer patients; C: Correlation of urinary DiAcSpm and serum CEA levels in gastric cancer patients; D: Correlation of urinary DiAcSpm and serum CEA levels in colorectal cancer patients. TPR: True positive rate; AUC: Area under the curve; FPR: False positive rate; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen 199; DiAcSpm: N1, N12-diacetylspermine.
Spearman correlation analysis revealed no significant correlation between urinary DiAcSpm and serum CEA in GC (r = 0.051, P = 0.749) (Figure 3C), whereas a weak correlation was observed in CRC (r = 0.267, P = 0.034) (Figure 3D).
Supplemental diagnostic performance of urinary DiAcSpm combined with CEA
To evaluate whether urinary DiAcSpm enhances CEA-based diagnosis, we analyzed the combined markers. The combined AUC for GC was significantly higher than that of CEA alone [AUCDiAcSpm + CEA = 0.755 (95%CI: 0.657-0.852) vs AUCCEA = 0.630 (95%CI: 0.511-0.749)], with sensitivity increasing to 94.74% but specificity decreasing to 50.00% (Figures 3A and 4A). For CRC, the combination also outperformed CEA alone [AUCDiAcSpm + CEA = 0.813 (95%CI: 0.739-0.887) vs AUC CEA = 0.794 (95%CI: 0.715-0.873)], with specificity rising to 58.73% and sensitivity remaining stable at 91.23% (Figures 3Band 4B).
Figure 4 Receiver operating characteristic curves of urinary N1, N12-diacetylspermine combined with serum carcinoembryonic antigen for gastric cancer and colorectal cancer.
A: In gastric cancer patients; B: In colorectal cancer patients. TPR: True positive rate; AUC: Area under the curve; FPR: False positive rate; DiAcSpm: N1, N12-diacetylspermine; CEA: Carcinoembryonic antigen; CI: Confidence interval.
Changes in urinary DiAcSpm after chemotherapy
Nine CRC patients and five GC patients were evaluated for changes in urinary DiAcSpm concentrations before and after chemotherapy. Among them, nine CRC patients achieved complete remission, and urinary DiAcSpm concentrations significantly decreased after chemotherapy (P = 0.031, Figure 5A). A reduction in urinary DiAcSpm levels was also observed in the five GC patients following chemotherapy; however, these changes did not reach statistical significance (P = 0.063,Figure 5B).
Figure 5 Changes of urinary N1, N12-diacetylspermine concentrations in patients with chemotherapy.
A: The changes of N1, N12-diacetylspermine in 9 colorectal cancer patients with chemotherapy; B: The changes of N1, N12-diacetylspermine in 5 gastric cancer patients with chemotherapy. aP < 0.05.
Correlation of clinical features and urinary DiAcSpm
We analyzed the association between urinary DiAcSpm concentrations and clinical features in patients with GC and CRC (Table 2). No significant correlation was observed between urinary DiAcSpm and age, sex, CEA, CA199, tumor-node-metastasis stage, lymph node metastasis, or tumor differentiation in either GC or CRC patients. However, high urinary DiAcSpm concentrations were significantly associated with distant metastasis in GC patients (P = 0.028). For CRC patients, those in the high urinary DiAcSpm group showed a trend toward more distant metastases, although this did not reach statistical significance (P = 0.064).
Table 2 The relationship between urinary N1, N12-diacetylspermine and clinical features in patients with gastric cancer and those with colorectal cancer, n (%).
In many countries, the incidence of GC and CRC is declining; however, an increasing trend has been observed among younger populations[23,24]. Patients with early-stage GC can achieve a 5-year overall survival exceeding 90%[25], whereas those with advanced GC involving local or distant metastases may experience a 5-year overall survival of only 5%-30%[26]. Even in the United States, more than 60% of GC patients present with local or distant metastases at diagnosis[26]. CRC has an overall 5-year survival rate of approximately 60%[27]. Notably, metastases are present in roughly 25% of patients at initial diagnosis, and nearly half of all CRC patients develop metastatic disease during the course of their illness[28]. For early-stage patients, surgery remains the primary curative approach, whereas for advanced disease, adjuvant therapies - including chemotherapy, radiotherapy, immunotherapy, and targeted therapy - play critical roles[29,30]. Therefore, early diagnosis is crucial to enable timely and effective treatment, which can significantly reduce mortality. Establishing reliable diagnostic methods for the early detection of GC and CRC is thus of great importance.
In recent years, urine-based liquid biopsy techniques leveraging metabolomics have provided new opportunities for early cancer diagnosis[31,32]. Polyamine metabolites are key regulators of cellular growth and development, and elevated polyamine levels are closely associated with enhanced cell proliferation[9,33,34]. As a terminal metabolite of polyamine metabolism, DiAcSpm is produced by tumor cells, excreted into the urine, and constitutes a minor fraction of human urinary polyamines[5]. Urinary DiAcSpm excretion is significantly elevated in various malignancies and is considered a potential noninvasive tumor biomarker. Notably, excretion levels are often markedly increased in specific cancers such as colorectal, breast, and prostate cancers, and a return to normal levels frequently correlates with complete clinical remission[35]. The findings of this study provide preliminary evidence supporting the clinical value of urinary DiAcSpm as a tumor marker in GC and CRC patients. First, elevated urinary DiAcSpm levels were specifically observed in GC patients compared with adults diagnosed with BGD and healthy controls. The decrease in urinary DiAcSpm levels after chemotherapy in the five GC patients was not statistically significant, likely due to the small sample size. To our knowledge, this study provides the first evidence of chemotherapy-associated changes in urinary DiAcSpm in GC patients. Second, urinary DiAcSpm concentrations in CRC patients were significantly higher than those in BGD patients and healthy controls, consistent with prior studies[13,17,36]. A systematic review and meta-analysis previously demonstrated that urinary DiAcSpm is significantly elevated in CRC patients compared with healthy controls[37]. This observation is further supported by tissue-level evidence showing that increased DiAcSpm in CRC is associated with acquisition of malignant characteristics[8]. Similarly, Mu et al[9] reported markedly higher DiAcSpm expression in CRC tissues. Mechanistically, cancer cells may produce DiAcSpm in parallel with elevated intracellular polyamine levels and active polyamine metabolism[8], potentially explaining the increased urinary concentrations observed in tumor patients.
Regarding diagnostic performance, although CRC patients exhibited elevated urinary DiAcSpm concentrations, its sensitivity was only 42.11%, which is relatively low. Previous studies have reported that urinary DiAcSpm detection rates in CRC patients across stages 0 + I, II, III, and IV were significantly higher than those of serum CEA or CA199[17]. Another study reported a DiAcSpm sensitivity of 69.6% in CRC patients, with CEA as the second most sensitive marker and CA199 the least[13]. Hiramatsu et al[38] reported that urinary DiAcSpm demonstrated significantly higher sensitivity (75.8%) than serum CEA (39.5%) and CA199 (14.1%) in CRC patients. Notably, GC currently lacks well-established urinary biomarkers, highlighting the potential reference value of DiAcSpm for GC diagnosis. Although DiAcSpm outperformed CEA in diagnostic efficacy for both GC and CRC, it is not recommended as a standalone marker for early detection. Instead, combining DiAcSpm with CEA improved diagnostic sensitivity for both cancers in the present study. However, this combined approach may result in a relatively high false-positive rate, potentially leading to unnecessary invasive endoscopic procedures. This limitation underscores the value of adopting a complementary diagnostic strategy in which DiAcSpm enhances, rather than replaces, CEA. Further validation in large-scale studies is required.
In addition to its diagnostic value, urinary DiAcSpm may be involved in tumor progression and serve as a prognostic indicator. Takahashi et al[16] reported that elevated urinary DiAcSpm was significantly associated with pathological stage, histological invasive factors, and adverse outcomes in patients with completely resected non-small cell lung cancer. Similarly, urinary DiAcSpm in breast cancer patients increased progressively with tumor size and was significantly higher in poorly differentiated tumors than in lower-grade counterparts[15]. A recent study indicated that urinary DiAcSpm is a useful tumor marker for the screening and prognostic follow-up of malignant lymphoma in children[20]. In Mu et al’s study[9], high DiAcSpm levels were significantly correlated with aggressive disease features such as advanced tumor-node metastasis, positive nodal involvement, and elevated Ki-67 proliferation index, suggesting that elevated DiAcSpm is associated with the malignant characteristics of CRC. In our study, high urinary DiAcSpm levels were significantly associated with the risk of distant metastasis in GC patients. Furthermore, CRC patients in the high DiAcSpm group were more likely to develop distant metastases, although this difference did not reach statistical significance. These findings suggest that urinary DiAcSpm is not only a diagnostic marker but may also be useful for assessing disease malignancy and prognosis.
Although DiAcSpm is likely related to the development of multiple cancers, the precise mechanisms underlying its function remain unclear. The oncogene c-MYC plays a central role in elevating urinary DiAcSpm concentrations[20], primarily through direct transcriptional regulation of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis[20,39]. As a well-established physiological target of MYC proto-oncogene, bHLH transcription factor (c-MYC)[40], increased MYC expression or amplification leads to ODC upregulation, which in turn elevates overall polyamine levels, including DiAcSpm[41,42]. This mechanistic cascade is particularly relevant in GC and CRC, where c-MYC is frequently overexpressed and promotes tumor progression through complex signaling networks[43-45]. Consequently, c-MYC activation results in accumulation of polyamine metabolites such as DiAcSpm, providing a strong theoretical basis for considering DiAcSpm as a biomarker associated with MYC-driven tumors. Supporting this link, a study demonstrated a direct correlation between increased c-MYC expression and higher urinary DiAcSpm concentrations[20]. In addition to serving as a metabolic byproduct, DiAcSpm also exhibits active biological functions in cancer progression. For example, Mu et al[9] demonstrated in vitro that DiAcSpm promotes proliferation of cancer cell lines via the miR-559/cystathionine-β-synthase axis. These findings suggest that DiAcSpm is not only a downstream metabolic indicator of MYC/ODC pathway activity but also a functional contributor to tumor growth, reinforcing its potential as a clinically relevant biomarker for GC and CRC.
Urine samples can be obtained noninvasively and conveniently, making them well suited for use in health examinations[46]. A simple and established method exists for quantifying urinary DiAcSpm[13]. Given these advantages, we propose incorporating urinary DiAcSpm into health examinations as a supplementary marker for early cancer screening. However, urinary DiAcSpm concentrations have also been reported to be elevated in conditions such as ulcerative colitis, benign prostatic hyperplasia, and systemic lupus erythematosus[13]. Furthermore, polyamine biosynthesis is closely linked to inflammatory processes[47,48]. Although no significant difference in DiAcSpm levels was observed between patients with gastritis and those with gastrointestinal polyps in this study, caution should be exercised when interpreting DiAcSpm concentrations in patients with these conditions or during active inflammation, as levels may be influenced by non-neoplastic pathologies.
This study has several limitations. First, the total number of participants in each group was relatively small, preventing stratified analyses; for example, we could not determine whether urinary DiAcSpm is associated with specific cancer stages. Second, the limited sample size for follow-up of GC and CRC patients may introduce potential biases. Third, a notable limitation of combining DiAcSpm and CEA in this study is the trade-off between improved sensitivity and an elevated false-positive rate, which could increase unnecessary invasive endoscopic procedures. Fourth, despite subgroup analyses, the overall sample size - particularly after stratification by cancer type, disease stage, and treatment modality - remains limited, potentially constraining the statistical robustness of some findings. Given these limitations, larger prospective studies are warranted to address them.
CONCLUSION
This study preliminarily demonstrated that urinary DiAcSpm is significantly elevated in patients with gastric and CRCs, and represents the first exploratory analysis of this marker in a GC population. Current evidence suggests that urinary DiAcSpm may have potential value as a tumor marker for both GC and CRC. Furthermore, its levels may correlate with tumor aggressiveness, indicating potential utility in prognostic assessment. However, these findings should be considered preliminary due to the limited sample size, and their clinical relevance requires validation in larger prospective cohorts.
ACKNOWLEDGEMENTS
The authors would like to thank Maidi Bio-Tech Co., Liaoning Province, China, for providing support and assistance.
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Creativity or innovation: Grade B, Grade B, Grade B
Scientific significance: Grade B, Grade B, Grade B
P-Reviewer: Liu YQ, Associate Chief Physician, Associate Professor, MD, PhD, China; Zhou Y, Academic Fellow, PhD, China S-Editor: Bai Y L-Editor: A P-Editor: Wang CH
