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It is often diagnosed at an advanced stage because of the absence of typical symptoms. Therefore, it is necessary to establish a screening method for the early detection of pancreatic cancer in high-risk individuals. This is a prospective validation study conducted in a cohort of 1033 Japanese individuals (male, n = 467, age = 63.3 \u00b1 11.5 years; female, n = 566, age = 64.2 \u00b1 10.6 years) to evaluate the use of salivary polyamines for screening pancreatic diseases and cancers. Patients with pancreatic cancer were not included; however, other pancreatic diseases were treated as positive cases for accuracy verification. Of the 135 individuals with elevated salivary polyamine markers, 66 had pancreatic diseases, such as chronic pancreatitis and pancreatic cysts, and 1 had gallbladder cancer. These results suggest that the salivary polyamine panel is a useful noninvasive pancreatic disease screening tool.<\/jats:p>","DOI":"10.3390\/ijms24032998","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T05:09:20Z","timestamp":1675400960000},"page":"2998","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Salivary Polyamines Help Detect High-Risk Patients with Pancreatic Cancer: A Prospective Validation Study"],"prefix":"10.3390","volume":"24","author":[{"given":"Daisuke","family":"Nose","sequence":"first","affiliation":[{"name":"Department of Cardiology, Fukuoka University Faculty of Medicine, Fukuoka 814-0180, Japan"},{"name":"Department of Cardiology, Fukuoka Heartnet Hospital, Fukuoka 819-0002, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3316-2543","authenticated-orcid":false,"given":"Masahiro","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, Tokyo Medical University, Shinjuku, Tokyo 160-8402, Japan"},{"name":"Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuneo","family":"Muta","sequence":"additional","affiliation":[{"name":"Department of Health Care Center, Imamura Hospital, Saga 841-0061, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Ichiro","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fukuoka University Faculty of Medicine, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","unstructured":"GBD 2017 Pancreatic Cancer Collaborators (2019). The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet. Gastroenterol. Hepatol., 4, 934\u2013947."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/hpb.12078","article-title":"2564 resected periampullary adenocarcinomas at a single institution: Trends over three decades","volume":"16","author":"He","year":"2014","journal-title":"HPB Off. J. Int. Hepato Pancreato Biliary Assoc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1093\/jnci\/djaa004","article-title":"Recent Trends in the Incidence and Survival of Stage 1A Pancreatic Cancer: A Surveillance, Epidemiology, and End Results Analysis","volume":"112","author":"Blackford","year":"2020","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.pan.2017.11.007","article-title":"Multicenter study of early pancreatic cancer in Japan","volume":"18","author":"Kanno","year":"2018","journal-title":"Pancreatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1038\/sj.bjc.6602619","article-title":"Type-II diabetes and pancreatic cancer: A meta-analysis of 36 studies","volume":"92","author":"Huxley","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00423-007-0266-2","article-title":"Tobacco and the risk of pancreatic cancer: A review and meta-analysis","volume":"393","author":"Iodice","year":"2008","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_8","first-page":"765","article-title":"Alcohol intake and pancreatic cancer risk: A pooled analysis of fourteen cohort studies","volume":"18","author":"Genkinger","year":"2009","journal-title":"Cancer Epidemiol.-Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1111\/j.1572-0241.1999.01075.x","article-title":"Incidence of cancer in the course of chronic pancreatitis","volume":"94","author":"Talamini","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1097\/00004836-198704000-00013","article-title":"Increased incidence of cancer in chronic pancreatitis","volume":"9","author":"Rocca","year":"1987","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1056\/NEJM199305203282001","article-title":"Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group","volume":"328","author":"Lowenfels","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S0140-6736(20)31318-0","article-title":"Chronic pancreatitis","volume":"396","author":"Beyer","year":"2020","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.3748\/wjg.v24.i43.4846","article-title":"Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes","volume":"24","author":"McGuigan","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.bpg.2010.02.007","article-title":"Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection","volume":"24","author":"Raimondi","year":"2010","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nrc1454","article-title":"Polyamines and cancer: Old molecules, new understanding","volume":"4","author":"Gerner","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1158\/2159-8290.CD-15-0507","article-title":"MYC, Metabolism, and Cancer","volume":"5","author":"Stine","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1080\/15384047.2021.2017223","article-title":"Target c-Myc to treat pancreatic cancer","volume":"23","author":"Ala","year":"2022","journal-title":"Cancer Biol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1038\/onc.2015.216","article-title":"MYC in pancreatic cancer: Novel mechanistic insights and their translation into therapeutic strategies","volume":"35","author":"Hessmann","year":"2016","journal-title":"Oncogene"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"18757","DOI":"10.1074\/jbc.TM118.003336","article-title":"Polyamine synthesis as a target of MYC oncogenes","volume":"293","author":"Bachmann","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Soda, K. (2011). The mechanisms by which polyamines accelerate tumor spread. J. Exp. Clin. Cancer Res. CR, 30.","DOI":"10.1186\/1756-9966-30-95"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Nakajima, T., Katsumata, K., Kuwabara, H., Soya, R., Enomoto, M., Ishizaki, T., Tsuchida, A., Mori, M., Hiwatari, K., and Soga, T. (2018). Urinary Polyamine Biomarker Panels with Machine-Learning Differentiated Colorectal Cancers, Benign Disease, and Healthy Controls. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030756"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.7150\/jca.16244","article-title":"Role of Urinary Biomarkers in the Diagnosis of Adenoma and Colorectal Cancer: A Systematic Review and Meta-Analysis","volume":"7","author":"Altobelli","year":"2016","journal-title":"J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1016\/j.cca.2010.07.018","article-title":"Evaluating the utility of N1,N12-diacetylspermine and N1,N8-diacetylspermidine in urine as tumor markers for breast and colorectal cancers","volume":"411","author":"Umemori","year":"2010","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/00006676-199003000-00001","article-title":"Polyamine concentrations in pancreatic tissue, serum, and urine of patients with pancreatic cancer","volume":"5","author":"Paprotny","year":"1990","journal-title":"Pancreas"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Asai, Y., Itoi, T., Sugimoto, M., Sofuni, A., Tsuchiya, T., Tanaka, R., Tonozuka, R., Honjo, M., Mukai, S., and Fujita, M. (2018). Elevated Polyamines in Saliva of Pancreatic Cancer. Cancers, 10.","DOI":"10.20944\/preprints201801.0092.v1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17060","DOI":"10.1038\/nrdp.2017.60","article-title":"Chronic pancreatitis","volume":"3","author":"Kleeff","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1001\/jama.2019.19411","article-title":"Diagnosis and Management of Chronic Pancreatitis: A Review","volume":"322","author":"Singh","year":"2019","journal-title":"Jama"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.pan.2018.05.008","article-title":"International consensus statements on early chronic Pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with The International Association of Pancreatology, American Pancreatic Association, Japan Pancreas Society, PancreasFest Working Group and European Pancreatic Club","volume":"18","author":"Whitcomb","year":"2018","journal-title":"Pancreatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1136\/gutjnl-2020-320723","article-title":"Identification and validation of a multivariable prediction model based on blood plasma and serum metabolomics for the distinction of chronic pancreatitis subjects from non-pancreas disease control subjects","volume":"70","author":"Adam","year":"2021","journal-title":"Gut"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"D\u00edaz, C., Jim\u00e9nez-Luna, C., Di\u00e9guez-Castillo, C., Mart\u00edn, A., Prados, J., Mart\u00edn-Ru\u00edz, J.L., Genilloud, O., Vicente, F., P\u00e9rez Del Palacio, J., and Caba, O. (2021). Untargeted Metabolomics for the Diagnosis of Exocrine Pancreatic Insufficiency in Chronic Pancreatitis. Med., 57.","DOI":"10.3390\/medicina57090876"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nissinen, S.I., Ven\u00e4l\u00e4inen, M., Kumpulainen, P., Roine, A., H\u00e4kkinen, M.R., Veps\u00e4l\u00e4inen, J., Oksala, N., and Rantanen, T. (2021). Discrimination between Pancreatic Cancer, Pancreatitis and Healthy Controls Using Urinary Polyamine Panel. Cancer Control J. Moffitt Cancer Cent., 28.","DOI":"10.1177\/10732748211039762"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s10549-019-05330-9","article-title":"Salivary metabolomics with alternative decision tree-based machine learning methods for breast cancer discrimination","volume":"177","author":"Murata","year":"2019","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3234","DOI":"10.1111\/cas.15472","article-title":"Salivary metabolomics with machine learning for colorectal cancer detection","volume":"113","author":"Kuwabara","year":"2022","journal-title":"Cancer Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Okuma, N., Saita, M., Hoshi, N., Soga, T., Tomita, M., Sugimoto, M., and Kimoto, K. (2017). Effect of masticatory stimulation on the quantity and quality of saliva and the salivary metabolomic profile. PloS ONE, 12.","DOI":"10.1371\/journal.pone.0183109"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cca.2018.11.030","article-title":"Effects of inter-day and intra-day variation on salivary metabolomic profiles","volume":"489","author":"Kawanishi","year":"2019","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1080\/14789450.2020.1846524","article-title":"Salivary metabolomics for cancer detection","volume":"17","author":"Sugimoto","year":"2020","journal-title":"Expert Rev. Proteom."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1042\/BST0350326","article-title":"Mechanisms of polyamine catabolism-induced acute pancreatitis","volume":"35","author":"Merentie","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e7697","DOI":"10.1073\/pnas.1710366114","article-title":"Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC","volume":"114","author":"Satoh","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1159\/000369887","article-title":"Does \u03b2-Catenin Cross-Regulate NF\u03baB Signalling in Pancreatic Cancer and Chronic Pancreatitis?","volume":"82","author":"Kumaran","year":"2015","journal-title":"Pathobiol. J. Immunopathol. Mol. Cell. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Carmicheal, J., Patel, A., Dalal, V., Atri, P., Dhaliwal, A.S., Wittel, U.A., Malafa, M.P., Talmon, G., Swanson, B.J., and Singh, S. (2020). Elevating pancreatic cystic lesion stratification: Current and future pancreatic cancer biomarker(s). Biochim. et Biophys. Acta (BBA) Rev. Cancer, 1873.","DOI":"10.1016\/j.bbcan.2019.188318"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1053\/j.gastro.2018.05.035","article-title":"Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance","volume":"155","author":"Canto","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00423-018-1740-8","article-title":"Main pancreatic duct dilation greater than 6 mm is associated with an increased risk of high-grade dysplasia and cancer in IPMN patients","volume":"404","author":"Ateeb","year":"2019","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1053\/j.gastro.2022.07.047","article-title":"Independent Validation and Assay Standardization of Improved Metabolic Biomarker Signature to Differentiate Pancreatic Ductal Adenocarcinoma From Chronic Pancreatitis","volume":"163","author":"Mahajan","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lindahl, A., Heuchel, R., Forshed, J., Lehti\u00f6, J., L\u00f6hr, M., and Nordstr\u00f6m, A. (2017). Discrimination of pancreatic cancer and pancreatitis by LC-MS metabolomics. Metab. Off. J. Metab. Soc., 13.","DOI":"10.1007\/s11306-017-1199-6"},{"key":"ref_45","first-page":"77","article-title":"Polyamine biomarkers as indicators of human disease","volume":"26","author":"Amin","year":"2021","journal-title":"Biomark. Biochem. Indic. Expo. Response Susceptibility Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Xu, H., Liu, R., He, B., Bi, C.W., Bi, K., and Li, Q. (2016). Polyamine Metabolites Profiling for Characterization of Lung and Liver Cancer Using an LC-Tandem MS Method with Multiple Statistical Data Mining Strategies: Discovering Potential Cancer Biomarkers in Human Plasma and Urine. Molecules, 21.","DOI":"10.3390\/molecules21081040"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.aca.2013.06.044","article-title":"Determination of polyamine metabolome in plasma and urine by ultrahigh performance liquid chromatography-tandem mass spectrometry method: Application to identify potential markers for human hepatic cancer","volume":"791","author":"Liu","year":"2013","journal-title":"Anal. Chim. Acta"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"DeFelice, B.C., Fiehn, O., Belafsky, P., Ditterich, C., Moore, M., Abouyared, M., Beliveau, A.M., Farwell, D.G., Bewley, A.F., and Clayton, S.M. (2022). Polyamine Metabolites as Biomarkers in Head and Neck Cancer Biofluids. Diagnostics, 12.","DOI":"10.3390\/diagnostics12040797"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cca.2015.10.032","article-title":"Diagnostic approach to breast cancer patients based on target metabolomics in saliva by liquid chromatography with tandem mass spectrometry","volume":"452","author":"Takayama","year":"2016","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1136\/gutjnl-2016-312432","article-title":"Metabolic biomarker signature to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis","volume":"67","author":"Mayerle","year":"2018","journal-title":"Gut"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.clinbiochem.2012.05.012","article-title":"Distinguishing pancreatic cancer from chronic pancreatitis and healthy individuals by (1)H nuclear magnetic resonance-based metabonomic profiles","volume":"45","author":"Zhang","year":"2012","journal-title":"Clin. Biochem."},{"key":"ref_52","first-page":"161","article-title":"Urinary 1H-NMR metabolomics can distinguish pancreatitis patients from healthy controls","volume":"14","author":"Lusczek","year":"2013","journal-title":"JOP J. Pancreas"},{"key":"ref_53","first-page":"454","article-title":"Physiological and environmental parameters associated with mass spectrometry-based salivary metabolomic profiles","volume":"9","author":"Sugimoto","year":"2013","journal-title":"Metab. Off. J. Metab. Soc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/B978-0-12-387042-1.00002-2","article-title":"Salivary transcriptome biomarkers in oral squamous cell cancer detection","volume":"55","author":"Brinkmann","year":"2011","journal-title":"Adv. Clin. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zhang, L., Xiao, H., Karlan, S., Zhou, H., Gross, J., Elashoff, D., Akin, D., Yan, X., Chia, D., and Karlan, B. (2010). Discovery and preclinical validation of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015573"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s00726-017-2378-5","article-title":"Effect of timing of collection of salivary metabolomic biomarkers on oral cancer detection","volume":"49","author":"Ishikawa","year":"2017","journal-title":"Amino Acids"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s10654-022-00945-7","article-title":"Smoking as the most important risk factor for chronic pancreatitis in the general population","volume":"38","author":"Hansen","year":"2023","journal-title":"Eur. J. Epidemiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Madeo, F., Eisenberg, T., Pietrocola, F., and Kroemer, G. (2018). Spermidine in health and disease. Science, 359.","DOI":"10.1126\/science.aan2788"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1097\/MPA.0000000000001513","article-title":"Clinical Practice Guidelines for Pancreatic Cancer 2019 From the Japan Pancreas Society: A Synopsis","volume":"49","author":"Okusaka","year":"2020","journal-title":"Pancreas"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Tomita, A., Mori, M., Hiwatari, K., Yamaguchi, E., Itoi, T., Sunamura, M., Soga, T., Tomita, M., and Sugimoto, M. (2018). Effect of storage conditions on salivary polyamines quantified via liquid chromatography-mass spectrometry. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-30482-x"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2998\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:23:21Z","timestamp":1760120601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2998"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,3]]},"references-count":60,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032998"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032998","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,3]]}}}