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 [Accepted]

Abstract PDF: 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 tumor-derived metabolites and proteins.
Materials and Methods
Plasma samples were collected under strict fasting and standardized processing protocols from patients diagnosed with PDAC, chronic pancreatitis (CP), and tumor-free controls (Ctrl). 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% CI: 0.92–1.00). At a fixed specificity of 96.8%, the panel yielded a sensitivity of 95.0% (95% CI: 85.0%–100.0%), significantly reducing the classification error from 30% with 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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Gastrointestinal cancer

Prevalence and Risk Factors of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma: Kum Hei Ryu, Sunhwa Park, Jung Won Chun, Eunhae Cho, Jongmun Choi, Dong-Eun Lee, Hyoeun Shim, Yun-Hee Kim, Sung-Sik Han, Sang-Jae Park, Sang Myung Woo, Sun-Young Kong; Cancer Res Treat. 2023;55(4):1303-1312. Published online April 3, 2023; DOI: https://doi.org/10.4143/crt.2023.291

Abstract PDF Supplementary Material PubReader ePub

Purpose
The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC.
Materials and Methods
Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed.
Results
PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035).
Conclusion
Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.

Citations

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