{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:07:34Z","timestamp":1789420054804,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"5th Beca Carmen Delgado\/Miguel P\u00e9rez-Mateo de AESPANC-ACANPAN","award":["25791\/001"],"award-info":[{"award-number":["25791\/001"]}]},{"name":"5th Beca Carmen Delgado\/Miguel P\u00e9rez-Mateo de AESPANC-ACANPAN","award":["PI19\/01231"],"award-info":[{"award-number":["PI19\/01231"]}]},{"name":"Spanish Health Institute Carlos III (ISCIII-FEDER)","award":["25791\/001"],"award-info":[{"award-number":["25791\/001"]}]},{"name":"Spanish Health Institute Carlos III (ISCIII-FEDER)","award":["PI19\/01231"],"award-info":[{"award-number":["PI19\/01231"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Pancreatic cancer is one of the deadliest tumours worldwide, and its poor prognosis is due to an inability to detect the disease at the early stages, thereby creating an urgent need to develop non-invasive biomarkers. P-element\u2013induced wimpy testis (PIWI) proteins work together with piwi-interacting RNAs (piRNAs) to perform epigenetic regulation and as such hold great potential as biomarkers for pancreatic cancer. PIWIL2 and PIWIL4 are associated with better prognosis, while PIWIL1 and PIWIL3 involvement appears to be associated with carcinogenesis. We aimed to discover PIWIL3- and PIWIL4-modulated piRNAs and determine their potential mechanisms in pancreatic cancer and the clinical implications. PIWIL3 or PIWIL4 was downregulated in pancreatic cancer-derived cell lines or in a non-tumour cell line. Differentially expressed piRNAs were analysed by next generation sequencing of small RNA. Nine fresh-frozen samples from solid human pancreases (three healthy pancreases, three intraductal papillary mucinous neoplasms, and three early-stage pancreatic cancers) were included in the sequencing analysis. Two piRNAs associated with PIWIL3 (piR-168112 and piR-162725) were identified in the neoplastic cells; in untransformed samples, we identified one piRNA associated with PIWIL4 (pir-366845). After validation in pancreatic cancer-derived cell lines and one untransformed pancreatic cell line, these piRNAs were evaluated in plasma samples from healthy donors (n = 27) or patients with pancreatic cancer (n = 45). Interestingly, piR-162725 expression identified pancreatic cancer patients versus healthy donors in liquid biopsies. Moreover, the potential of the serum carbohydrate antigen 19-9 (CA19-9) biomarker to identify pancreatic cancer patients was greatly enhanced when combined with piR-162725 detection. The enhanced diagnostic potential for the early detection of pancreatic cancer in liquid biopsies of these new small non-coding RNAs will likely improve the prognosis and management of this deadly cancer.<\/jats:p>","DOI":"10.3390\/jcm11247310","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T03:23:49Z","timestamp":1670556229000},"page":"7310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A Novel PiRNA Enhances CA19-9 Sensitivity for Pancreatic Cancer Identification by Liquid Biopsy"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0262-8945","authenticated-orcid":false,"given":"Weiyao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510085, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Gonzalez-Gonzalez","sequence":"additional","affiliation":[{"name":"Microbiology Laboratory, Clinico San Carlos University Hospital, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Sanz-Criado","sequence":"additional","affiliation":[{"name":"Translational Oncology Division, OncoHealth Institute, Health Research Institute Fundacion Jimenez Diaz, Fundacion Jimenez Diaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Garcia-Carbonero","sequence":"additional","affiliation":[{"name":"Translational Oncology Division, OncoHealth Institute, Health Research Institute Fundacion Jimenez Diaz, Fundacion Jimenez Diaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Celdran","sequence":"additional","affiliation":[{"name":"General and Hepatobiliary Surgery Unit, Fundacion Jimenez Diaz University Hospital, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Villarejo-Campos","sequence":"additional","affiliation":[{"name":"General and Hepatobiliary Surgery Unit, Fundacion Jimenez Diaz University Hospital, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4099-9421","authenticated-orcid":false,"given":"Pablo","family":"Minguez","sequence":"additional","affiliation":[{"name":"Genetics and Genomics Department, IIS-Fundacion Jimenez Diaz, Universidad Autonoma de Madrid (IIS-FJD, UAM), Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Bioinformatics Unit, IIS-FJD, UAM, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-7391","authenticated-orcid":false,"given":"Roberto","family":"Pazo-Cid","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Custodia","family":"Garcia-Jimenez","sequence":"additional","affiliation":[{"name":"Area of Physiology, Department of Basic Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University, 28922 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Orta-Ruiz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Cl\u00ednico San Carlos, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), CIBERONC, 28040 Madrid, Spain"},{"name":"Department of Medical Oncology, MD Anderson Cancer Center Madrid, 28033 Madrid, Spain"},{"name":"Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223 Pozuelo de Alarc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Garcia-Foncillas","sequence":"additional","affiliation":[{"name":"Translational Oncology Division, OncoHealth Institute, Health Research Institute Fundacion Jimenez Diaz, Fundacion Jimenez Diaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9007-828X","authenticated-orcid":false,"given":"Javier","family":"Martinez-Useros","sequence":"additional","affiliation":[{"name":"Translational Oncology Division, OncoHealth Institute, Health Research Institute Fundacion Jimenez Diaz, Fundacion Jimenez Diaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain"},{"name":"Area of Physiology, Department of Basic Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University, 28922 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"ref_1","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. 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