Cancer Research and Treatment

Original Articles

Extracellular Vesicle-Derived Adenosine as a Diagnostic Metabolic Biomarker for Pancreatic Ductal Adenocarcinoma: Tao Xia, Wenhui Ouyang, Jie Wang, Jinjing Wang, Yiping Mou, Zhengquan Yang, Hezhi Fang, Shanying Gui; Received May 12, 2025 Accepted September 11, 2025 Published online September 24, 2025; DOI: https://doi.org/10.4143/crt.2025.510 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Current non-invasive diagnostic tools for pancreatic ductal adenocarcinoma (PDAC) exhibit limited sensitivity and specificity. This study aimed to identify more accurate plasma biomarkers by profiling extracellular vesicles (EVs), which are enriched in tumorderived metabolites and proteins.
Materials and Methods
Plasma samples were collected under strict fasting and standardized processing protocols from patients diagnosed with PDAC, chronic pancreatitis, and tumor-free controls. EVs were isolated from these plasma samples and subjected to comprehensive metabolomic and proteomic profiling to identify disease-specific biomarkers.
Results
A biomarker panel comprising adenosine, adenine, and N-acetylneuraminate (AAN) demonstrated outstanding diagnostic performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.968 (95% confidence interval [CI], 0.92 to 1.00). At a fixed specificity of 96.8%, the panel yielded a sensitivity of 95.0% (95% CI, 85.0% to 100.0%), significantly reducing the classification error from 30% with carbohydrate antigen 19-9 (CA19-9) to 5% with the AAN panel. Among individual markers, adenosine alone showed high diagnostic power (AUC, 0.952), correlating with increased expression of 5′-nucleotidase ecto (NT5E), indicative of elevated extracellular purine metabolism. Importantly, these features were unique to the EV compartment and outperformed markers derived from total plasma metabolite profiles.
Conclusion
The integration of EV metabolomics and proteomics revealed enhanced purine metabolism, particularly elevated extracellular adenosine, as a distinctive hallmark of PDAC. EV-derived adenosine emerges as a highly promising non-invasive biomarker with superior diagnostic accuracy compared to CA19-9.

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Predictive Value of Preoperative Serum CEA, CA19-9 and CA125 Levels for Peritoneal Metastasis in Patients with Gastric Carcinoma: Gun Ick Hwang, Chang Hak Yoo, Byung Ho Sohn, Jun Ho Shin, Yong Lai Park, Heung Dai Kim, Yong Shin Kim, Won Kon Han, Won Kil Pae; Cancer Res Treat. 2004;36(3):178-181. Published online June 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.3.178

Purpose

Peritoneal metastasis is a crucial factor for the prognosis in gastric cancer, but its diagnosis is difficult before laparotomy. This study analyzed the usefulness of diagnostic imaging and various tumor markers in the detection of peritoneal metastasis in gastric cancer.

Materials and Methods

The sera from 768 patients with gastric cancer were measured for CEA, CA19-9 and CA125 levels using a commercial immunoradiometric assay. All the patients underwent diagnostic imaging with computed tomography (CT) and ultrasound (US) before laparotomy.

Results

Preoperative levels of CEA, CA19-9 and CA125 were above the cut-off levels in 15.4%, 8.7% and 5.7% of all cases, respectively. Eighty-eight patients were diagnosed with peritoneal metastasis by laparotomy. CT and US revealed peritoneal dissemination in 15 of 88 patients (17%). Among the three tumor markers, CA19-9 and CA125 showed similar detection rates of peritoneal metastasis (37.5% and 38.6%, respectively). In particular, the serum CA125 levels showed the best sensitivity (38.6%), specificity (98.4%), and diagnostic accuracy (91.5%), and the highest odd ratio (24.46, 95% CI: 11.17~53.57) for predicting peritoneal metastasis among the markers tested. CEA did not add significant predictive information (p=0.471).

Conclusion

Preoperative serum CA19-9 and CA125 levels may provide a predictable value in determining peritoneal metastasis in patients with gastric cancer.

Citations

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Prognostic Value of CEA and CA19 - 9 in Serum and Peritoneal Washing Fluid in Gastric Carcinoma: Sang Uk Han, Yong Kwan Cho, Seong Woo Hong, Young Ae Lim, Yun Sik Kwak, Myung Wook Kim; J Korean Cancer Assoc. 1998;30(5):869-878.

Abstract PDF: PURPOSE
The clinical significance of preoperative serum levels of CEA and CA19-9, levels of CEA and CA19-9 in peritoneal washing fluid and free cancer cells in peritoneal washing fluid in gastric cancer patients were evaluated in this study.
MATERIALS AND METHODS
Serum and peritoneal levels of CEA and CA19-9 and peritoneal washing cytology in 115 patients with gastric cancer were analyzed with respect to the prognostic factors using univariate and multivariate analysis.
RESULTS
Positive rate of serum CEA and CA19-9 was 16.5%, 13.0%. And that of peritoneal washing CEA, CA19-9 and cytology was 15.7%, 7.8% and 9.6%. A univariate analysis showed that tumor markets in serum and peritoneal washing fluid and peritoneal washing cytology had significant correlations with the progression of the tumors, and patients with positive serum or peritoneal tumor markers had poorer survival after operation than did the patients with negative tumor markers. But in a multivariate analysis showed that only peritoneal CA19-9 was an independent risk factor. And combination of these five markers provided rnore predictable prognostic informations in a multivariate analysis.
CONCLUSION
Combination of serum or peritoneal levels of CEA, CA19-9 and washing cytology appeared to be a useful marker for managing gastric cancer patients.

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