{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T12:02:03Z","timestamp":1788177723281,"version":"build-2803163510"},"reference-count":25,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The role and underlying mechanisms of synaptophysin-like-1 (SYPL1), a neuroendocrine-associated protein, in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study aims to assess the diagnostic potential of SYPL1 as a serum biomarker for both resectable PDAC (rPDAC) and metastatic PDAC (mPDAC) located at the head of the pancreas. Additionally, the SYPL1 levels were monitored in PDAC patients who underwent surgical resection, with follow-up measurements taken 6 months postoperatively. Method: We analyzed serum SYPL1 in healthy controls (n = 67), rPDAC patients (n = 39), mPDAC patients (n = 22), and rPDAC patients (6-month postoperative) (n = 20) (due to factors such as relocation or death, 20 patients were included instead of 39 patients) by ELISA. Results: The SYPL-1 levels showed significant differences across the groups (controls: 7.43 \u00b1 3.32, PC: 15.89 \u00b1 2.00, mPDAC: 20.01 \u00b1 4.03, p &lt; 0.001). Both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were significantly greater in cancer groups compared to the healthy group. In patients who underwent surgical resection, the SYPL-1 levels showed a significant decrease 6 months after surgery (p &lt; 0.001). Strong correlations were observed between tumor markers, with CA19-9 showing a positive correlation with CEA in both rPDAC (r = 0.550, p &lt; 0.001) and mPDAC (r = 0.623, p = 0.002), while SYPL-1 demonstrated a negative correlation with CEA (r = \u22120.530, p = 0.009) in mPDAC. Receiver operating characteristic (ROC) analysis revealed excellent diagnostic performance for SYPL-1 in distinguishing both rPDAC (AUC = 0.965) and mPDAC (AUC = 0.985) from healthy controls, achieving superior accuracy compared to conventional markers CEA and CA19-9. Conclusions: Serum SYPL-1 emerges as a promising biomarker for the diagnosis and monitoring of rPDAC and mPDAC. Its significantly elevated levels in cancer groups, coupled with its marked decrease following surgical resection, suggest that SYPL-1 could play a critical role in both initial diagnosis and post-treatment surveillance. The strong correlations observed between SYPL-1, CEA, and CA19-9 further support its potential utility in a multi-marker panel. Notably, SYPL-1 demonstrated superior diagnostic accuracy compared to conventional markers, with high AUC values indicating its excellent ability to distinguish rPDAC and mPDAC from healthy controls. These findings highlight the need for further investigation to validate SYPL-1 as a reliable, non-invasive biomarker that could enhance early detection, prognosis, and treatment monitoring in rPDAC.<\/jats:p>","DOI":"10.3390\/jcm14113719","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T09:29:36Z","timestamp":1748338176000},"page":"3719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synaptophysin-like-1: A Novel Serum Diagnostic Marker for Pancreatic Ductal Adenocarcinoma Screening, Early Diagnosis, and Prognosis Prediction"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0315-8044","authenticated-orcid":false,"given":"Sefa","family":"Ergun","sequence":"first","affiliation":[{"name":"Department of General Surgery, Cerrahpa\u015fa Faculty of Medicine, Istanbul University-Cerrahpasa, 34320 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taskin","family":"Avci","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Cerrahpa\u015fa Faculty of Medicine, Istanbul University-Cerrahpasa, 34320 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8893-2926","authenticated-orcid":false,"given":"Seyma","family":"Dumur","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, 34403 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6186-8722","authenticated-orcid":false,"given":"Yasemin","family":"Pekmezci","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Cerrahpa\u015fa Faculty of Medicine, Istanbul University-Cerrahpasa, 34320 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1347-8498","authenticated-orcid":false,"given":"Hafize","family":"Uzun","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, 34403 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5925-2128","authenticated-orcid":false,"given":"U\u011furcan","family":"Say\u0131l\u0131","sequence":"additional","affiliation":[{"name":"Department of Public Health, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34320 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yagmur Ozge Turac","family":"Kosem","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Cerrahpa\u015fa Faculty of Medicine, Istanbul University-Cerrahpasa, 34320 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osman","family":"Simsek","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Cerrahpa\u015fa Faculty of Medicine, Istanbul University-Cerrahpasa, 34320 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salih","family":"Pekmezci","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Cerrahpa\u015fa Faculty of Medicine, Istanbul University-Cerrahpasa, 34320 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3892\/ijo.2022.5383","article-title":"Cellular metabolism in pancreatic cancer as a tool for prognosis and treatment (Review)","volume":"61","author":"Trnka","year":"2022","journal-title":"Int. J. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5763","DOI":"10.2147\/OTT.S253418","article-title":"Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Adenocarcinoma Cells\u2014Role of Snail, Slug and Twist and Small Molecule Inhibitors","volume":"13","author":"Aydemir","year":"2020","journal-title":"Onco. Targets Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1259\/0007-1285-59-698-182","article-title":"Cutaneous seeding of pancreatic carcinoma by fineneedle aspiration biopsy","volume":"59","author":"Russell","year":"1986","journal-title":"Br. J. Radiol."},{"key":"ref_4","unstructured":"Tempero, M.A., Malafa, M.P., Asbun, H., Behrman, S.W., and Benson, A.B. (2015). Pancreatic Adenocarcinoma, National Comprehensive Cancer Network. Version 2."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/bjc.2012.569","article-title":"Hyaluronan, fluid pressure, and stromal resistance in pancreas cancer","volume":"108","author":"Provenzano","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"439","DOI":"10.6004\/jnccn.2021.0017","article-title":"Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology","volume":"19","author":"Tempero","year":"2021","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1002\/cac2.12204","article-title":"Early screening and diagnosis strategies of pancreatic cancer: A comprehensive review","volume":"41","author":"Yang","year":"2021","journal-title":"Cancer Commun."},{"key":"ref_8","first-page":"1","article-title":"Diagnostic and therapeutic recommendations in pancreatic ductal adenocarcinoma. Recommendations of the Working Group of the Polish Pancreatic Club","volume":"14","author":"Winter","year":"2019","journal-title":"Prz. Gastroenterol."},{"key":"ref_9","first-page":"340","article-title":"The clinical utility of CA 19-9 in pancreatic adenocarcinoma: Diagnostic and prognostic updates","volume":"13","author":"Poruk","year":"2013","journal-title":"Curr. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1074\/jbc.275.3.2029","article-title":"Pantophysin is a phosphoprotein component of adipocyte transport vesicles and associates with GLUT4-containing vesicles","volume":"275","author":"Brooks","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Song, Y., Sun, X., Duan, F., He, C., Wu, J., Huang, X., Xing, K., Sun, S., Wang, R., and Xie, F. (2020). SYPL1 Inhibits Apoptosis in Pancreatic Ductal Adenocarcinoma via Suppression of ROS-Induced ERK Activation. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01482"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.clinbiochem.2022.02.009","article-title":"Evaluation of fecal SYPL1 as a diagnostic biomarker in colorectal cancer","volume":"103","author":"Shu","year":"2022","journal-title":"Clin. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.3892\/or.2017.5843","article-title":"SYPL1 overexpression predicts poor prognosis of hepatocellular carcinoma and is associated with epithelial-mesenchymal transition","volume":"38","author":"Chen","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S969","DOI":"10.4103\/jcrt.JCRT_730_16","article-title":"Identification of differentiated functional modules in papillary thyroid carcinoma by analyzing differential networks","volume":"14","author":"Yang","year":"2018","journal-title":"J. Cancer Res. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.cca.2020.05.048","article-title":"Serum SYPL1 is a promising diagnostic biomarker for colorectal cancer","volume":"509","author":"Liu","year":"2020","journal-title":"Clin. Chim. Acta."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"273","DOI":"10.5937\/jomb0-46198","article-title":"Clinical significance of serum synaptophysin-like 1 protein levels in breast cancer","volume":"43","author":"Kosem","year":"2024","journal-title":"J. Med. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, B., Shao, B., Liu, Z., Wang, L., and Hong, B. (2025). A Novel Circ_0004104\/MiR-493-5p\/SYPL1 Cascade Contributes to Colorectal Cancer Progression. J. Biochem. Mol. Toxicol., 39.","DOI":"10.1002\/jbt.70226"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/jhbp.205","article-title":"Preoperative evaluation of the confluent drainage veins to the gastrocolic trunk of Henle: Understanding the surgical vascular anatomy during pancreaticoduodenectomy","volume":"22","author":"Miyazawa","year":"2015","journal-title":"J. Hepatobiliary Pancreat. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bestari, M.B., Joewono, I.R., and Syam, A.F. (2024). A Quest for Survival: A Review of the Early Biomarkers of Pancreatic Cancer and the Most Effective Approaches at Present. Biomolecules, 14.","DOI":"10.20944\/preprints202402.0955.v1"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pekmezci, Y., Ergun, S., Turgut, B.C., Dumur, S., Sayili, U., Uzun, H., Pekmezci, S., and Velidedeoglu, M. (2025). The Role of Resolvin D1 in the Differential Diagnosis of Pancreatic Ductal Adenocarcinoma and Acute Pancreatitis: A Case-Control Study. Medicina, 61.","DOI":"10.3390\/medicina61020168"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Nurmi, A.M., Mustonen, H.K., Stenman, U.H., Sepp\u00e4nen, H.E., and Haglund, C.H. (2021). Combining CRP and CA19-9 in a novel prognostic score in pancreatic ductal adenocarcinoma. Sci. Rep., 11.","DOI":"10.1038\/s41598-020-80778-0"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1159\/000520063","article-title":"Impact of Acute Inflammation on the Survival Outcomes of Patients with Resected Pancreatic Ductal Adenocarcinoma","volume":"38","author":"Saad","year":"2021","journal-title":"Dig. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"97248","DOI":"10.5306\/wjco.v16.i2.97248","article-title":"Pancreatic cancer: Future challenges and new perspectives for an early diagnosis","volume":"16","author":"Cocca","year":"2025","journal-title":"World J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"rs3","DOI":"10.1126\/scisignal.2003305","article-title":"A genome-wide siRNA screen reveals positive and negative regulators of the NOD2 and NF-\u03baB signaling pathways","volume":"6","author":"Warner","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ramesh, R.P.G., Yasmin, H., Ponnachan, P., Al-Ramadi, B., Kishore, U., and Joseph, A.M. (2025). Phenotypic heterogeneity and tumor immune microenvironment directed therapeutic strategies in pancreatic ductal adenocarcinoma. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1573522"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/11\/3719\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:40:24Z","timestamp":1760031624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/11\/3719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,26]]},"references-count":25,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["jcm14113719"],"URL":"https:\/\/doi.org\/10.3390\/jcm14113719","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,26]]}}}