{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:24:45Z","timestamp":1790832285454,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies in the world, for which the mortality is almost as high as the disease incidence and is predicted to be the second\u2010highest cause of cancer\u2010related deaths by 2030. These cancerous tumors consist of diversified gene expressions within the different cellular subpopulations that include neoplastic ductal cells, cancer\u2010associated fibroblasts, and immune cells, all of which collectively facilitate cellular heterogeneity in the PDAC tumor microenvironment (TME). Active intratumoral interaction within the cell populations in TME induces the proliferation of cancerous cells, accounting for tumorigenesis and rapid metastasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review will focus on novel findings uncovering PDAC heterogeneity in different cellular subpopulations using single\u2010cell RNA\u2010sequencing (scRNA\u2010seq) and other single\u2010cell analysis technologies. It will further explore the emerging role of single\u2010cell technologies in assessing the role of different subpopulations of neoplastic ductal cells, cancer\u2010associated fibroblasts, and immune cells in PDAC progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Conclusion<\/jats:title>\n                    <jats:p>The application of scRNA\u2010seq in PDAC has started to unveil associations between disease progression and heterogeneity in pancreatic TME and could influence future PDAC treatment. Recent advances in scRNA\u2010seq have uncovered comprehensive analyses of heterogeneous ecosystems present within the TME. These emerging findings underpins further need for a more in\u2010depth understanding of intratumoral heterogeneity in the PDAC microenvironment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.6407","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:52:17Z","timestamp":1691110337000},"page":"18020-18031","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Heterogeneous tumor microenvironment in pancreatic ductal adenocarcinoma: An emerging role of single\u2010cell analysis"],"prefix":"10.1002","volume":"12","author":[{"given":"Sooin","family":"Byeon","sequence":"first","affiliation":[{"name":"Northern Clinical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"},{"name":"Kolling Institute of Medical Research, University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taymin","family":"du Toit\u2010Thompson","sequence":"additional","affiliation":[{"name":"Northern Clinical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"},{"name":"Kolling Institute of Medical Research, University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Gillson","sequence":"additional","affiliation":[{"name":"Northern Clinical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"},{"name":"Kolling Institute of Medical Research, University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Gill","sequence":"additional","affiliation":[{"name":"Northern Clinical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"},{"name":"Kolling Institute of Medical Research, University of Sydney  Sydney New South Wales Australia"},{"name":"Australian Pancreatic Centre  Sydney New South Wales Australia"},{"name":"Cancer Diagnosis and Pathology Group Kolling Institute of Medical Research  St Leonards New South Wales Australia"},{"name":"NSW Health Pathology, Department of Anatomical Pathology Royal North Shore Hospital  St Leonards New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaswinder S.","family":"Samra","sequence":"additional","affiliation":[{"name":"Northern Clinical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"},{"name":"Australian Pancreatic Centre  Sydney New South Wales Australia"},{"name":"Upper GI Surgical Unit Royal North Shore Hospital and North Shore Private Hospital  St Leonards New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anubhav","family":"Mittal","sequence":"additional","affiliation":[{"name":"Northern Clinical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"},{"name":"Australian Pancreatic Centre  Sydney New South Wales Australia"},{"name":"Upper GI Surgical Unit Royal North Shore Hospital and North Shore Private Hospital  St Leonards New South Wales Australia"},{"name":"The University of Notre Dame Australia  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2900-8845","authenticated-orcid":false,"given":"Sumit","family":"Sahni","sequence":"additional","affiliation":[{"name":"Northern Clinical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"},{"name":"Kolling Institute of Medical Research, University of Sydney  Sydney New South Wales Australia"},{"name":"Australian Pancreatic Centre  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i43.4846"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v27.i27.4298"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00141-0"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9082440"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.22"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.20892\/j.issn.2095-3941.2019.0252"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0b013e31827459b6"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.12.042"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00309-X"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.04445"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/101.6.684"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MP.0000086072.56290.FB"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903387"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.19"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v12.i2.173"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-020-0530-4"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-316451"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2012.29"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140692"},{"issue":"4","key":"e_1_2_12_21_1","article-title":"Characterization of myeloid leukocytes and soluble mediators in pancreatic cancer: importance of myeloid\u2010derived suppressor cells","volume":"4","author":"Karakhanova S","year":"2015","journal-title":"Onco Targets Ther"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26059-4"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000363RR"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2344"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3398"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16965"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-019-0010-1"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1955"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.648917"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2022.100258"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01134-8"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1248"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2022.215834"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-021-00366-y"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-019-0195-y"},{"key":"e_1_2_12_36_1","article-title":"RNA isolation from mouse pancreas: a ribonuclease\u2010rich tissue","volume":"90","author":"Azevedo\u2010Pouly AC","year":"2014","journal-title":"J Vis Exp"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209648"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.11.010"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4407"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103315"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0300-1"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0094"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.06.017"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-021-00271-4"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21550-4"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-019-0822-6"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13101760"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-020-00121-4"},{"key":"e_1_2_12_49_1","first-page":"2021","article-title":"High\u2010plex multiomic analysis in ffpe tissue at single\u2010cellular and subcellular resolution by spatial molecular imaging","author":"He S","year":"2021","journal-title":"bioRxiv"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.6407","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.6407","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.6407","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:04:10Z","timestamp":1786968250000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.6407"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,3]]},"references-count":48,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1002\/cam4.6407"],"URL":"https:\/\/doi.org\/10.1002\/cam4.6407","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,3]]},"assertion":[{"value":"2023-04-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}