Serum MicroRNA-196, -200 and -423 Improve Diagnostics and Differentiate Pancreatic Ductal Adenocarcinoma From Chronic Pancreatitis
Jazyk angličtina Země Česko Médium print
Typ dokumentu časopisecké články
PubMed
41329540
PubMed Central
PMC12746859
DOI
10.33549/physiolres.935586
PII: 935586
Knihovny.cz E-zdroje
- MeSH
- chronická pankreatitida * krev diagnóza genetika MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- duktální karcinom slinivky břišní * krev diagnóza genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- nádorové biomarkery * krev MeSH
- nádory slinivky břišní * krev diagnóza genetika MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mikro RNA * MeSH
- MIRN196 microRNA, human MeSH Prohlížeč
- nádorové biomarkery * MeSH
Sustained poor survival rate in pancreatic ductal adenocarcinoma (PDAC) calls for an earlier diagnosis to assure curative treatment. New powerful biomarkers are necessary because the currently used CA19-9 is not sensitive enough to distinguish PDAC, especially from chronic pancreatitis (CP). Expressions of miRNA-21, -30 -192, -196, -200, and -423 were measured in 77 patients with PDAC, 26 patients with CP and 64 non-cancer/non-CP subjects (39 patients with type 2 diabetes mellitus and 25 control healthy persons). Eleven patients with PDAC had CP at the background. The expressions of all microRNAs were significantly 1.4-3.7 times higher in the PDAC group compared to non-cancer/non-CP subjects and 2.2-6.1 times higher compared to CP patients. No difference in miRNA expressions was found between diabetic and non-diabetic patients. CA19-9 did not distinguish CP from PDAC patients with the history of CP, whereas all six miRNAs were able to do it. Adding miR-196, -200 and -423 to current marker CA19-9 improved sensitivity by 7 % (to 93 %) and specificity by 8 % (to 89 %). MicroRNA-423 could significantly distinguish PDAC from CP with both sensitivity and specificity 96 %. Panel of six miRNAs could be used as reliable marker in differentiating PDAC from chronic pancreatitis with the most impressive difference in miR-196 and miR-423. Key words microRNA " Pancreatic ductal adenocarcinoma " Chronic pancreatitis " Biomarker " CA19-9.
Zobrazit více v PubMed
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. doi: 10.3322/caac.21442. PubMed DOI
Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, Dimagno JP, et al. International Pancreatitis Study Group. Pancreatitis and the risk of pancreatic cancer. N Engl J Med. 1993;328:1433–1437. doi: 10.1056/NEJM199305203282001. PubMed DOI
Juthani R, Manne A. Blood-based biomarkers in pancreatic ductal adenocarcinoma: developments over the last decade and what holds for the future- a review. Front Oncology. 2025;15:1555963. doi: 10.3389/fonc.2025.1555963. PubMed DOI PMC
Wolrab D, Jirásko R, Cífková E, Höring M, Mei D, Chocholoušková M, Peterka O, et al. Lipidomic profiling of human serum enables detection of pancreatic cancer. Nat Commun. 2022;13:124. doi: 10.1038/s41467-021-27765-9. PubMed DOI PMC
Hasani F, Masrour M, Khamaki S, Jazi K, Hosseini S, Heidarpour H, Namazee M. Diagnostic and Prognostic Accuracy of MiRNAs in Pancreatic Cancer: A Systematic Review and Meta-Analysis. J Cell Molec Med. 2025;29:e70337. doi: 10.1111/jcmm.70337. PubMed DOI PMC
Gayral M, Jo S, Hanoun N, Vignolle-Vidoni A, Lulka H, Delpu Y, Meulle A, et al. MicroRNAs as emerging biomarkers and therapeutic targets for pancreatic cancer. World J Gastroenterol. 2014;20:11199–11209. doi: 10.3748/wjg.v20.i32.11199. PubMed DOI PMC
Al-Temaimi R, Abdulkarim B, Al-Ali A, John B, Mallik MK, Kapila K. Analysis of Candidate miRNAs’ Expression in Pancreatic Cancer. Cancer Med. 2024;13:e70400. doi: 10.1002/cam4.70400. PubMed DOI PMC
Przybyszewski O, Mik M, Nowicki M, Kusinski M, Mikołajczyk-Solinska M, Sliwinska A. Using microRNAs Networks to Understand Pancreatic Cancer-A Literature Review. Biomedicines. 2024;12:1713. doi: 10.3390/biomedicines12081713. PubMed DOI PMC
Khan IA, Saraya A. Circulating MicroRNAs as Noninvasive Diagnostic and Prognostic Biomarkers in Pancreatic Cancer: A Review. J Gastroint Cancer. 2023;54:720–730. doi: 10.1007/s12029-022-00877-1. PubMed DOI
Powrózek T, Otieno MO, Maffeo D, Frullanti E, Martinez-Useros J. Blood circulating miRNAs as pancreatic cancer biomarkers: An evidence from pooled analysis and bioinformatic study. Int J Biol Macromol. 2025;308:142469. doi: 10.1016/j.ijbiomac.2025.142469. PubMed DOI
Cote GA, Gore AJ, McElyea S, Heathers LE, Xu H, Sherman S, Korc M. A pilot study to develop a diagnostic test for pancreatic ductal adenocarcinoma based on differential expression of select miRNA in plasma and bile. Am J Gastroenterol. 2014;109:1942–1952. doi: 10.1038/ajg.2014.331. PubMed DOI PMC
Mok ETY, Chitty JL, Cox TR. miRNAs in pancreatic cancer progression and metastasis. Clin Exp Metastasis. 2024;41:163–186. doi: 10.1007/s10585-023-10256-0. PubMed DOI PMC
Xia T, Chen XY, Zhang YN. MicroRNAs as biomarkers and perspectives in the therapy of pancreatic cancer. Molec Cell Biochem. 2021;476:4191–4203. doi: 10.1007/s11010-021-04233-y. PubMed DOI
Škrha P, Hořínek A, Pazourková E, Hajer J, Frič P, Škrha J, Andel M. Serum microRNA-196 and microRNA-200 in pancreatic ductal adenocarcinoma of patients with diabetes mellitus. Pancreatology. 2016;16:839–843. doi: 10.1016/j.pan.2016.05.005. PubMed DOI
Singh N, Khan IA, Rashid S, Rashid S, Roy S, Kaushik K, Kumar A, et al. MicroRNA Signatures for Pancreatic Cancer and Chronic Pancreatitis. Pancreas. 2024;53:e260–e267. doi: 10.1097/MPA.0000000000002297. PubMed DOI
Guo S, Qin H, Liu K, Wang H, Bai S, Liu S, Shao Z, et al. Blood small extracellular vesicles derived miRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis. Clin Transl Med. 2021;11:e520. doi: 10.1002/ctm2.520. PubMed DOI PMC
American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2010;33(Suppl 1):S62–S69. doi: 10.2337/dc10-S062. PubMed DOI PMC
Bitterlich N, Schneider J. Cut-off-independent Tumour Marker Evaluation Using ROC Approximation. Anticancer Res. 2007;27:4305–4310. PubMed
Frič P, Šedo A, Škrha J, Busek P, Laclav M, Skrha P, Zavoral M. Early detection of sporadic pancreatic cancer: time for change. Eur J Gastroenterol Hepatol. 2017;29:885–891. doi: 10.1097/MEG.0000000000000904. PubMed DOI
Škrha J, Frič P, Bušek P, Škrha P, Šedo A. RODRIGO, editor. Advances in Pancreatic Cancer. InTechOpen; Rijeka: 2018. Sporadic pancreatic cancer - glucose homeostasis and pancreatogenic Type 3 diabetes; pp. 53–72. DOI
Lopez NE, Prendergast C, Lowy AM. Borderline resectable pancreatic cancer: Definitions and management. World J Gastroenterol. 2014;20:10740–10751. doi: 10.3748/wjg.v20.i31.10740. PubMed DOI PMC
Wagner M, Redaelli C, Seiler CA, Seiler CA, Friess H, Buchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004;91:586–594. doi: 10.1002/bjs.4484. PubMed DOI
Bedi MMS, Gandhi MD, Jacob G, Lekha V, Venugopal A, Ramesh H. CA 19-9 to differentiate benign and malignant masses in chronic pancreatitis: is there any benefit? Indian J Gastroenterol. 2009;28:24–27. doi: 10.1007/s12664-009-0005-4. PubMed DOI
Poruk KE, Gay DZ, Brown K, Mulvihill JD, Boucher KM, Scaife CL, Firpo MA, Mulvihill SJ. The Clinical Utility of CA 19-9 in Pancreatic Adenocarcinoma: Diagnostic and Prognostic Updates. Curr Mol Med. 2013;13:340–351. doi: 10.2174/156652413805076876. PubMed DOI PMC
Kawai M, Fukuda A, Otomo R 38 co-authors. Early detection of pancreatic cancer by comprehensive serum miRNA sequencing with automated machine learning. Br J Cancer. 2024;131:1158–1168. doi: 10.1038/s41416-024-02794-5. PubMed DOI PMC
Franklin O, Jonsson P, Billing O, Lundberg E, Öhlund D, Nyström H, Lundin C, Antti H, Sund M. Plasma Micro-RNA Alterations Appear Late in Pancreatic Cancer. Ann Surg. 2018;267:775–781. doi: 10.1097/SLA.0000000000002124. PubMed DOI PMC
Xue Y, Abou Tayoun AN, Abo KM, Pipas JM, Gordon SR, Gardner TB, Barth RJ, Jr, et al. MicroRNAs as diagnostic markers for pancreatic ductal adenocarcinoma and its precursor, pancreatic intraepithelial neoplasm. Cancer Genet. 2013;206:217–221. doi: 10.1016/j.cancergen.2013.05.020. PubMed DOI
Slater EP, Strauch K, Rospleszcz S, Ramaswamy A, Esposito I, Klöppel G, Matthäi E, et al. MicroRNA-196a and -196b as Potential Biomarkers for the Early Detection of Familial Pancreatic Cancer. Transl Oncol. 2014;7:464–471. doi: 10.1016/j.tranon.2014.05.007. PubMed DOI PMC
Hernandez YG, Lucas AL. MicroRNA in pancreatic ductal adenocarcinoma and its precursor lesions. World J Gastrointest Oncol. 2016;8:18–29. doi: 10.4251/wjgo.v8.i1.18. PubMed DOI PMC
Ke RS, Lv LZ, Zhang SY, Zhang FX, Jiang Y. Functional mechanism and clinical implications of MicroRNA-423 in human cancers. Cancer Med. 2020;9:9036–9051. doi: 10.1002/cam4.3557. PubMed DOI PMC
Zhou Y, Liu Y, Zong Z, Huang H, Liang L, Yang X, Xin M, et al. Rapid and sensitive detection of exosomal microRNAs by terahertz metamaterials. Spectrochim Acta A Mol Biomol Spectrosc. 2025;330:125745. doi: 10.1016/j.saa.2025.125745. PubMed DOI
Cao Z, Liu C, Xu JW, You L, Wang C, Lou W, Sun B, et al. Plasma microRNA panels to diagnose pancreatic cancer: Results from a multicenter study. Oncotarget. 2016;7:41575–41583. doi: 10.18632/oncotarget.9491. PubMed DOI PMC
Le Large TYS, Meijer LL, Prado MM, Kazemier G, Frampton AE, Giovannetti E. Circulating microRNAs as diagnostic biomarkers for pancreatic cancer. Expert Rev Mol Diagn. 2015;15:1525–1529. doi: 10.1586/14737159.2015.1112273. PubMed DOI
Liu J, Gao J, Yiqi D, Li Z, Ren Y, Gu J, Wang X, et al. Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer. Int J Cancer. 2012;131:683–691. doi: 10.1002/ijc.26422. PubMed DOI
Khan IA, Rashid S, Singh N, Rashid S, Singh V, Gunjan D, Das P, et al. Panel of serum miRNAs as potential 3on invasive biomarkers for pancreatic ductal adenocarcinoma. Sci Rep. 2021;11:2824. doi: 10.1038/s41598-021-82266-5. PubMed DOI PMC
Flammang I, Reese M, Ströse AJ, Yang Z, Eble JA, Dhayat SA. Tumor-Suppressive miR-192-5p Has Prognostic Value in Pancreatic Ductal Adenocarcinoma. Cancers. 2020;12:1693. doi: 10.3390/cancers12061693. PubMed DOI PMC
Azadinejad H, Farhadi Rad M, Babaeizad A, Samadi A. MicroRNA profiling in pancreatic cancer and chronic pancreatitis: Novel insights and pathway analysis. Human Gene. 2025;44:201410. doi: 10.1016/j.humgen.2025.201410. DOI
Luan X, Wang X, Bian G, Li X, Gao Z, Liu Z, Zhang Z, et al. Exosome applications for the diagnosis and treatment of pancreatic ductal adenocarcinoma: An update (Review) Oncol Rep. 2025;53:13. doi: 10.3892/or.2024.8846. PubMed DOI PMC
Xu B, Chen Y, Peng M, Zheng JH, Zuo Ch. Exploring the potential of exosomes in diagnosis and drug delivery for pancreatic ductal adenocarcinoma. Int J Cancer. 2023;152:110–122. doi: 10.1002/ijc.34195. PubMed DOI PMC
Tiwari PK, Shanmugam P, Karn V, Gupta S, Mishra R, Rustagi S, Chouhan M, et al. Extracellular Vesicular miRNA in Pancreatic Cancer: From Lab to Therapy. Cancers. 2024;16:2179. doi: 10.3390/cancers16122179. PubMed DOI PMC
Wlodarczyk B, Durko L, Walczak K, Talar-Wojnarowska R, Malecka-Wojciesko E. Select Endocrine Disorders and Exosomes in Early PDACDiagnosis. Int J Mol Sci. 2024;25:12159. doi: 10.3390/ijms252212159. PubMed DOI PMC
Otey CA, Rachlin A, Moza M, Arneman D, Carpen O. The Palladin/Myotilin/Myopalladin Family of Actin-Associated Scaffolds. Int Rev Cytol. 2005;246:31–58. doi: 10.1016/S0074-7696(05)46002-7. PubMed DOI
Pogue-Geile KL, Chen R, Bronner MP, Crnogorac-Jurcevic T, Moyes KW, Dowen S, Otey CA, et al. Palladin Mutation Causes Familial Pancreatic Cancer and Suggests a New Cancer Mechanism. PLoS Med. 2006;3:e516. doi: 10.1371/journal.pmed.0030516. PubMed DOI PMC
Salaria SN, Illei P, Sharma R, Walter KM, Klein AP, Eshleman JR, Maitra A, et al. Palladin is overexpressed in the non-neoplastic stroma of infiltrating ductal adenocarcinomas of the pancreas, but is only rarely overexpressed in neoplastic cells. Cancer Biol Ther. 2007;6:324–328. doi: 10.4161/cbt.6.3.3904. PubMed DOI PMC
Sato D, Tsuchikawa T, Mitsuhashi T, Hatanaka Y, Marukawa K, Morooka A, Nakamura T, et al. Stromal Palladin Expression Is an Independent Prognostic Factor in Pancreatic Ductal Adenocarcinoma. PLoS One. 2016;11:e0152523. doi: 10.1371/journal.pone.0152523. PubMed DOI PMC
Alvarez-Teijeiro S, Menendez ST, Angeles Villaronga M, Rodrigo JP, Manterola L, de Villalaín L, de Vicente JC, et al. Dysregulation of Mir-196b in Head and Neck Cancers Leads to Pleiotropic Effects in the Tumor Cells and Surrounding Stromal Fibroblasts. Sci Rep. 2017;7:17785. doi: 10.1038/s41598-017-18138-8. PubMed DOI PMC
Xiong M, Wang P, Pan B, Nie J, Wang S, He B. The diagnostic and prognostic values of microRNA-196a in cancer. Biosci Rep. 2021;41:BSR20203559. doi: 10.1042/BSR20203559. PubMed DOI PMC
Buck A, Buchholz M, Wagner M, Adler G, Gress T, Ellenrieder V. The tumor suppressor KLF11 mediates a novel mechanism in transforming growth factor beta-induced growth inhibition that is inactivated in pancreatic cancer. Mol Cancer Res. 2006;4:861–872. doi: 10.1158/1541-7786.MCR-06-0081. PubMed DOI
Ellenrieder V, Buck A, Harth A, Jungert K, Buchholz M, Adler G, Urrutia R, Gress TM. KLF11 mediates a critical mechanism in TGF-beta signaling that is inactivated by Erk-MAPK in pancreatic cancer cells. Gastroenterology. 2004;127:607–620. doi: 10.1053/j.gastro.2004.05.018. PubMed DOI
Sanchez-Cid L, Pons M, Lozano JJ, Rubio N, Guerra-Rebollo M, Soriano A, Paris-Coderch L, et al. MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells. Oncotarget. 2017;8:83384–83406. doi: 10.18632/oncotarget.20698. PubMed DOI PMC
Yu L, Wu D, Gao H, Balic JJ, Tsykin A, Han TS, Liu YD, et al. Clinical utility of a STAT3-regulated microRNA-200 family signature with prognostic potential in early gastric cancer. Clin Cancer Res. 2018;24:1459–1472. doi: 10.1158/1078-0432.CCR-17-2485. PubMed DOI
Arunkumar G, Rao AKDM, Manikandan M, Rao HPS, Subbiah S, Ilangovan R, Murugan AK, Munirajan AK. Dysregulation of miR-200 family microRNAs and epithelial-mesenchymal transition markers in oral squamous cell carcinoma. Oncol Lett. 2018;15:649–657. doi: 10.3892/ol.2017.7296. PubMed DOI PMC
O’Brien SJ, Carter JV, Burton JF, Oxford BG, Schmidt MN, Hallion JC, Galandiuk S. The role of the miR-200 Family in Epithelial-Mesenchymal Transition in Colorectal Cancer: A Systematic Review. Int J Cancer. 2018;142:2501–2511. doi: 10.1002/ijc.31282. PubMed DOI
Koutsaki M, Libra M, Spandidos DA, Zaravinos A. The miR-200 family in ovarian cancer. Oncotarget. 2017;8:66629–66640. doi: 10.18632/oncotarget.18343. PubMed DOI PMC
Si LB, Tian H, Yue WM, Li L, Li SH, Gao C, Qi L. Potential use of microRNA-200c as a prognostic marker in non-small cell lung cancer. Oncol Lett. 2017;14:4325–4330. doi: 10.3892/ol.2017.6667. PubMed DOI PMC
Lee JS, Ahn YH, Won HS, Sun DS, Kim YH, Ko YH. Prognostic Role of the MicroRNA-200 Family in Various Carcinomas: A Systematic Review and Meta-Analysis. Biomed Res Int. 2017;2017:1928021. doi: 10.1155/2017/1928021. PubMed DOI PMC
Belgardt BF, Ahmed K, Spranger M, Latreille M, Denzler R, Kondratiuk N, von Meyenn F, et al. The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes. Nat Med. 2015;21:619–627. doi: 10.1038/nm.3862. PubMed DOI
Lohajová Behulová R, Bugalová A, Bugala J, Struhárňanská E, Šafranek M, Juráš I. Circulating Exosomal miRNAs as a Promising Diagnostic Biomarker in Cancer. Physiol Res. 2023;72(Suppl 3):S193–S207. doi: 10.33549/physiolres.935153. PubMed DOI PMC