Indexing
CÁC SỐ TỪ 2011-2023
Tạp chí Y Dược Học
Abstract
Background: Pancreatic cancer is difficult to diagnose definitively due to limitations in accessing the tumor for tissue sampling. Droplet digital PCR (ddPCR), with its ability to detect serum circulating tumor DNA (ctDNA), shows potential for diagnosing this disease without biopsy. Therefore, we conducted this study aimed to: (1) Determine rates of KRAS codon 12/13 and 61 mutations in ctDNA in patients with pancreatic cancer and pancreatic benign diseases using droplet digital PCR; (2) Investigate diagnostic value of KRAS mutations in combination with traditional biomarkers (CA 19-9, CEA) in pancreatic cancer. Materials and methods: The study was conducted on 99 patients, which were divided into three groups: pancreatic cancer, benign pancreatic tumors/cysts and chronic pancreatitis, were measured mutKRASctDNA using ddPCR. Results: Rates of positive mutKRAS ctDNA were 72.5%, 25.0% and 7.1%, respectively. Mutations at codon 12/13 accounted for 70.6%, mutations at codon 61 accounted for only 3.9% in the pancreatic cancer group. The combination of KRAS MAF in ctDNA and CA 19-9 had a better diagnostic value for pancreatic cancer than that of CA 19-9 alone, with AUC = 0.883, p = 0.0333. Conclusion: Rates of KRAS mutations in ctDNA in pancreatic cancer is significantly higher than those in benign pancreatic diseases, mostly in codon 12/13. The diagnostic value of KRAS MAF in ctDNA in pancreatic cancer was not inferior to CA 19-9, but combining both markers was better than using only CA 19-9.
| Published | 2026-06-28 | |
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| Issue | Vol. 16 No. 3 (2026) | |
| Section | Original Articles | |
| DOI | 10.34071/jmp.2026.3.993 | |
| Keywords | pancreatic cancer, KRAS, ctDNA, ddPCR, CA 19-9, CEA ung thư tụy, KRAS, ctDNA, ddPCR, CA 19-9, CEA |
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Copyright (c) 2026 Hue Journal of Medicine and Pharmacy
Muñoz AR, Chakravarthy D, Gong J, Halff GA, Ghosh R, Kumar AP. Pancreatic Cancer: Current Status and Challenges. Curr Pharmacol Rep 2017;3:396–408.
Narayanan G, Hevert EA, Venkat SR. Pancreatic Cancer. In: Kapoor BS, Lorenz JM, editors. Digestive Disease Interventions. Stuttgart: Thieme Verlag; 2018. page 206–14.
Vareedayah AA, Alkaade S, Taylor JR. Pancreatic Adenocarcinoma. Mo Med 2018; 115:230–5.
Hu JX, Lin YY, Zhao CF, Chen WB, Liu QC, Li QW, et al. Pancreatic cancer: A review of epidemiology, trend, and risk factors. World J Gastroenterol 2021; 27:4298–321.
Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin 2025; 75:10–45.
Ballehaninna UK, Chamberlain RS. Serum CA 19-9 as a Biomarker for Pancreatic Cancer-A Comprehensive Review. Indian J Surg Oncol 2011; 2:88–100.
Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, et al. ASCO 2006 Update of Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer. Journal of Clinical Oncology 2006; 24:5313–27.
Jakob Z, Günther SC, Marie-Christine S, Sebesta C. Clinical Relevance of Tumor Markers in Gastrointestinal Cancers: A Critical Analysis and Literature Review. JSM Clinical Oncology and Research 2024;12:1–9.
Zhang Y, Yang J, Li H, Wu Y, Zhang H, Chen W. Tumor markers CA19-9, CA242 and CEA in the diagnosis of pancreatic cancer: a meta-analysis. Int J Clin Exp Med 2015; 8:11683.
Reitz D, Gerger A, Seidel J, Kornprat P, Samonigg H, Stotz M, et al. Combination of tumour markers CEA and CA19-9 improves the prognostic prediction in patients with pancreatic cancer. J Clin Pathol 2015; 68:427–33.
Wang M, Bu H, Luo W, Zeng X, Chen G, He Y, et al. CA19-9, CEA and PIVKA-Ⅱ as a novel panel of serum markers for diagnosis of pancreatic cancer. Clin Biochem 2025; 137:110902.
Forbes SA, Beare D, Boutselakis H, Bamford S, Bindal N, Tate J, et al. COSMIC: somatic cancer genetics at high-resolution. Nucleic Acids Res 2017; 45:D777–83.
Wang ZY, Ding XQ, Zhu H, Wang RX, Pan XR, Tong JH. KRAS Mutant Allele Fraction in Circulating Cell-Free DNA Correlates With Clinical Stage in Pancreatic Cancer Patients. Front Oncol 2019; 9:487904.
Huerta M, Roselló S, Sabater L, Ferrer A, Tarazona N, Roda D, et al. Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review. Cancers 2021; 13:994.
Gardner TB, Adler DG, Forsmark CE, Sauer BG, Taylor JR, Whitcomb DC. ACG Clinical Guideline: Chronic Pancreatitis. American Journal of Gastroenterology 2020; 115:322–39.
Shimizu K, Ito T, Irisawa A, Ohtsuka T, Ohara H, Kanno A, et al. Evidence-based clinical practice guidelines for chronic pancreatitis 2021. Journal of Gastroenterology 2022; 57:709–24.
Anaizi A, Hart PA, Conwell DL. Diagnosing Chronic Pancreatitis. Dig Dis Sci 2017; 62:1713–20.
Hà Thị Minh Thi, Ngô Thị Diệu Hương, Lê Phan Tưởng Quỳnh, Trương Xuân Long, Trần Văn Huy, Nguyễn Thị Mai Ngân, ctv. Ứng dụng kỹ thuật Droplet Digital PCR để phát hiện đột biến gene KRAS của DNA khối u lưu hành trong máu ở bệnh nhân ung thư tuỵ. Tạp chí Y Dược Huế 2025; 15:93–9.
Ko SW, Kim TH, Song TJ, Kim SH, Seo DW, Yoon JH, et al. Prognosis and Clinical Characteristics of Patients with Pancreatic Ductal Adenocarcinoma Diagnosed by Endoscopic Ultrasonography but Indeterminate on Computed Tomography. Gut Liver 2022; 16:474–82.
Shi Y, Gao F, Li Y, Tao S, Yu B, Liu Z, et al. Differentiation of benign and malignant solid pancreatic masses using magnetic resonance elastography with spin-echo echo planar imaging and three-dimensional inversion reconstruction: a prospective study. European Radiology 2017; 28:936–45.
Olesen SS, Mortensen LH, Zinck E, Becker U, Drewes AM, Nøjgaard C, et al. Time trends in incidence and prevalence of chronic pancreatitis: A 25-year population-based nationwide study. UEG Journal 2021; 9:82–90.
Masamune A, Kikuta K, Kume K. Alcohol and Smoking in Chronic Pancreatitis. In: The Pancreas: an Integrated Textbook of Basic Science, Medicine, and Surgery, Fourth Edition. Wiley; 2023. page 396–403.
Salvatore T, Marfella R, Rizzo MR, Sasso FC. Pancreatic cancer and diabetes: A two-way relationship in the perspective of diabetologist. International Journal of Surgery 2015; 21:S72–7.
Goodarzi MO, Petrov MS, Andersen DK, Hart PA. Diabetes in chronic pancreatitis: Risk factors and natural history. Curr Opin Gastroenterol 2021; 37:526–31.
Kim MK, Woo SM, Park B, Yoon KA, Kim YH, Joo J, et al. Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma. Clin Chem 2018; 64:726–34.
Hadano N, Murakami Y, Uemura K, Hashimoto Y, Kondo N, Nakagawa N, et al. Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer. British Journal of Cancer 2016; 115:59–65.
Lin M, Alnaggar M, Liang S, Chen J, Xu K, Dong S, et al. Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer. Cellular Physiology and Biochemistry 2018; 47:1556–64.
Sivapalan L, Kocher HM, Ross-Adams H, Chelala C. Molecular profiling of ctDNA in pancreatic cancer: Opportunities and challenges for clinical application. Pancreatology 2021; 21:363–78.
Buscail L, Bournet B, Cordelier P. Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer. Nat Rev Gastroenterol Hepatol 2020; 17:153–68.
Jain M, Atayan D, Rakhmatullin T, Dakhtler T, Popov P, Kim P, et al. Cell-Free Tumor DNA Detection-Based Liquid Biopsy of Plasma and Bile in Patients with Various Pancreatic Neoplasms. Biomedicines 2024; 12:220.
Yang F, Li L, Kong XY. The Positive Feedback Loop Between Inflammation and Mutant KRAS Genes Promotes Malignant Transformation in Chronic Pancreatitis. Cancer Screening and Prevention 2022; 1:39–46.
Nitschke C, Tölle M, Walter P, Meiner K, Goetz M, Kropidlowski J, et al. KRAS and GNAS mutations in cell-free DNA and in circulating epithelial cells in patients with intraductal papillary mucinous neoplasms—an observational pilot study. Mol Oncol 2025; 19:2144–53.
Hata T, Mizuma M, Motoi F, Omori Y, Ishida M, Nakagawa K, et al. GNAS mutation detection in circulating cell-free DNA is a specific predictor for intraductal papillary mucinous neoplasms of the pancreas, especially for intestinal subtype. Scientific Reports 2020; 10:17761.
Tempero MA, Malafa MP, Al-Hawary M, Behrman SW, Benson AB, Cardin DB, et al. Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network 2021; 19:439–57.
Ni XG, Bai XF, Mao YL, Shao YF, Wu JX, Shan Y, et al. The clinical value of serum CEA, CA19-9, and CA242 in the diagnosis and prognosis of pancreatic cancer. European Journal of Surgical Oncology 2005; 31:164–9.
Donizeti de MEIRA-JÚNIOR J, Nogueira COSTA T, Luis MONTAGNINI A, Carlos NAHAS S, Jukemura J, Donizeti de Meira-Júnior J, et al. ELEVATED CA 19-9 IN AN ASYMPTOMATIC PATIENT: WHAT DOES IT MEAN? ABCD. Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) 2022; 35:e1687.
Ermiah E, Eddfair M, Abdulrahman O, Elfagieh M, Jebriel A, Al-Sharif M, et al. Prognostic value of serum CEA and CA19-9 levels in pancreatic ductal adenocarcinoma. Mol Clin Oncol 2022; 17:1–10.
Xing H, Wang J, Wang Y, Tong M, Hu H, Huang C, et al. Diagnostic Value of CA 19-9 and Carcinoembryonic Antigen for Pancreatic Cancer: A Meta-Analysis. Gastroenterol Res Pract 2018; 2018:8704751.
Kane LE, Mellotte GS, Mylod E, O’Brien RM, O’Connell F, Buckley CE, et al. Diagnostic Accuracy of Blood-based Biomarkers for Pancreatic Cancer: A Systematic Review and Meta-analysis. Cancer Research Communications 2022; 2:1229–43.