{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T10:27:30Z","timestamp":1780914450735,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Classification and risk stratification of pancreatic cysts are challenging because of limited radiographic and cytomorphologic features. Although molecular profiling has emerged as an ancillary test for pancreatic cyst fluid (PCF), additional high\u2010sensitivity and \u2010specificity biomarkers are still needed for improved classification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, PCF from 93 patients, including intraductal papillary mucinous neoplasms (<jats:italic>n<\/jats:italic>\u00a0=\u00a065), mucinous cystic neoplasms (<jats:italic>n<\/jats:italic>\u00a0=\u00a09), serous cystadenomas (<jats:italic>n<\/jats:italic>\u00a0=\u00a09), pancreatic cyst not otherwise specified (<jats:italic>n<\/jats:italic>\u00a0=\u00a08), and pseudocysts (<jats:italic>n<\/jats:italic>\u00a0=\u00a02), were evaluated for biomarkers. Molecular profiling by next\u2010generation sequencing was performed, and a subset of the cases (<jats:italic>n<\/jats:italic>\u00a0=\u00a032) were interrogated with 2083 microRNAs (miRNAs) to evaluate their use for pancreatic cyst risk stratification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As independent PCF biomarkers in 32 cases with histologic diagnoses, three miRNAs performed significantly better than mutant <jats:italic>KRAS<\/jats:italic>, mutant <jats:italic>GNAS<\/jats:italic>, carcinoembryonic antigen (CEA), and serum carbohydrate antigen 19\u20109 (CA19\u20109) in discriminating high\u2010risk from low\u2010risk cysts. The three elevated miRNAs in combination with mutant <jats:italic>KRAS<\/jats:italic>, mutant <jats:italic>GNAS<\/jats:italic>, and serum CA19\u20109 displayed similar diagnostic performance (miR\u20104461: area under the curve [AUC], 0.950; 95% confidence interval [CI], 0.800\u20131; miR\u20106723\u20105p: AUC, 0.958; 95% CI, 0.850\u20131; miR\u20106755\u20103p: AUC, 0.942; 95% CI, 0.816\u20131) in discriminating high\u2010risk from low\u2010risk cysts, when compared to mutant <jats:italic>KRAS<\/jats:italic>, mutant <jats:italic>GNAS<\/jats:italic>, CEA, and serum CA19\u20109 (AUC, 0.950; 95% CI, 0.825\u20131). In the absence of CA19\u20109, the three\u2010marker panel of <jats:italic>KRAS<\/jats:italic>, <jats:italic>GNAS<\/jats:italic>, and miRNAs showed marginally improved performance compared with <jats:italic>KRAS<\/jats:italic>, <jats:italic>GNAS<\/jats:italic>, and CEA, which highlights the potential utility of miRNAs as biomarkers in PCF analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings demonstrate that a multiomics biomarker approach with elevated PCF miRNAs with mutant <jats:italic>KRAS<\/jats:italic>, mutant <jats:italic>GNAS<\/jats:italic>, and serum CA19\u20109 may help in better detecting high\u2010risk cysts for early clinical intervention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.70008","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T12:34:38Z","timestamp":1742387678000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["An integrated multi\u2010omics biomarker approach using molecular profiling and microRNAs for evaluation of pancreatic cyst fluid"],"prefix":"10.1002","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3812-5477","authenticated-orcid":false,"given":"Mohamed H.","family":"Maher","sequence":"first","affiliation":[{"name":"Division of Pathology and Laboratory Medicine Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"},{"name":"South Egypt Cancer Institute Assiut University  Assiut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7542-5201","authenticated-orcid":false,"given":"Warapen","family":"Treekitkarnmongkol","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3431-9955","authenticated-orcid":false,"given":"Sayak","family":"Ghatak","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine Department of Hematopathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0964-9287","authenticated-orcid":false,"given":"Jianliang","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0126-2646","authenticated-orcid":false,"given":"Suyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4565-1534","authenticated-orcid":false,"given":"Tristian","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6763-9736","authenticated-orcid":false,"given":"Dzifa Y.","family":"Duose","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8269-854X","authenticated-orcid":false,"given":"Michael P.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5166-4937","authenticated-orcid":false,"given":"Tony Y.","family":"Hu","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Diagnostics Department of Cell and Molecular Biology Tulane University School of Medicine  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6102-4925","authenticated-orcid":false,"given":"Mark W.","family":"Hurd","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"},{"name":"Sheikh Ahmed Center for Pancreatic Cancer Research The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8677-4741","authenticated-orcid":false,"given":"Pamela L.","family":"Paris","sequence":"additional","affiliation":[{"name":"UCSF Helen Diller Family Comprehensive Cancer Center University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6876-2752","authenticated-orcid":false,"given":"Kimberly S.","family":"Kirkwood","sequence":"additional","affiliation":[{"name":"UCSF Helen Diller Family Comprehensive Cancer Center University of California San Francisco  San Francisco California USA"},{"name":"Section of Hepatopancreaticobiliary Surgery Division of Surgical Oncology Department of Surgery University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7923-9978","authenticated-orcid":false,"given":"Anirban","family":"Maitra","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"},{"name":"Sheikh Ahmed Center for Pancreatic Cancer Research The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7133-0221","authenticated-orcid":false,"given":"Rajyalakshmi","family":"Luthra","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"},{"name":"Division of Pathology and Laboratory Medicine Department of Hematopathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-6246","authenticated-orcid":false,"given":"Subrata","family":"Sen","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-7701","authenticated-orcid":false,"given":"Sinchita","family":"Roy\u2010Chowdhuri","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"},{"name":"Division of Pathology and Laboratory Medicine Department of Anatomical Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2015.08.038"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2024.02.041"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21344"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2024.100510"},{"key":"e_1_2_8_6_1","first-page":"629","article-title":"Revisiting the performance of cyst fluid carcinoembryonic antigen as a diagnostic marker for pancreatic mucinous cysts: a comprehensive 20\u2010year institutional review","volume":"73","author":"Kwan MC","year":"2024","journal-title":"Gut"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2023.05.005"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.07.041"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.02.013"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.11.052"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102303.2009.00664.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.09.028"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201014\u20100513"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21775"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gie.2015.06.047"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2015.08.002"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102016\u2010313586"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav4772"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/sla.0000000000005904"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastha.2024.08.002"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940\u20106207.capr\u201020\u20100303"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2014.09.029"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201012\u20100035"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2016.61"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.7554\/elife.05005"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav1741"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26999"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.08.006"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2014.11.029"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12112573"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22946"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201012\u20100035"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay1984"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb9601"}],"container-title":["Cancer Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncy.70008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T12:39:32Z","timestamp":1760272772000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncy.70008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/cncy.70008"],"URL":"https:\/\/doi.org\/10.1002\/cncy.70008","archive":["Portico"],"relation":{},"ISSN":["1934-662X","1934-6638"],"issn-type":[{"value":"1934-662X","type":"print"},{"value":"1934-6638","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,19]]},"assertion":[{"value":"2024-10-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70008"}}