{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T04:32:28Z","timestamp":1776486748954,"version":"3.51.2"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005614","name":"BC Cancer Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005614","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014823","name":"VGH and UBC Hospital Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014823","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2021,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The mixture of epithelial and stromal components in pancreatic ductal adenocarcinoma (PDAC) may confound sequencing\u2010based studies of tumor gene expression. Virtual microdissection has been suggested as a bioinformatics approach to segment the aforementioned components, and subsequent prognostic gene sets have emerged from this research. We examined the prognostic signature from the epithelial gene set of one such study using laser capture microdissected (LCM) epithelial samples. We also examined this gene set in matched stromal samples to determine whether prognostic findings were specific to the epithelium. LCM samples from 48 long\u2010term and 48 short\u2010term PDAC survivors were obtained. The resultant epithelial and stromal components were subjected to direct mRNA quantification using a 49 gene published PDAC classifier. Component\u2010specific unsupervised hierarchical clustering was used to derive groups and survival differences were quantified. Immunohistochemical validation of particular genes was performed in an independent cohort. Clustering in the epithelial component yielded prognostic differences in univariable analysis (<jats:italic>P<\/jats:italic>= .02), but those differences were not significant when controlled for other clinicopathologic covariates (<jats:italic>P<\/jats:italic>= .06). Clustering in the stromal component yielded prognostic differences that persisted in the presence of other clinicopathologic covariates (<jats:italic>P<\/jats:italic>= .0005). Validation of selected genes in the epithelium (KRT6A\u2014negative prognostic [<jats:italic>P<\/jats:italic>= .004]) and stroma (LY6D\u2014improved prognostic [<jats:italic>P<\/jats:italic>= .01] and CTSV\u2014negative prognostic [<jats:italic>P<\/jats:italic>= .0002]) demonstrated statistical independence in multivariable analysis. Although the genes used in this study were originally identified as being representative of the epithelial component of PDAC, their expression in the stroma appears to provide additional information that may aid in improved prognostication.<\/jats:p>","DOI":"10.1002\/ijc.33304","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T19:24:59Z","timestamp":1600716299000},"page":"481-491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Stroma vs epithelium\u2010enhanced prognostics through histologic stratification in pancreatic ductal adenocarcinoma"],"prefix":"10.1002","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1332-7881","authenticated-orcid":false,"given":"Steve E.","family":"Kalloger","sequence":"first","affiliation":[{"name":"Pancreas Centre BC Vancouver General Hospital Vancouver British Columbia Canada"},{"name":"Department of Pathology and Laboratory Medicine University of British Columbia Vancouver British Columbia Canada"},{"name":"School of Population and Public Health University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna M.","family":"Karasinska","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC Vancouver General Hospital Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin S.","family":"Keung","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC Vancouver General Hospital Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle L.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC Vancouver General Hospital Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Chow","sequence":"additional","affiliation":[{"name":"Genetic Pathology Evaluation Centre University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongxia","family":"Gao","sequence":"additional","affiliation":[{"name":"Genetic Pathology Evaluation Centre University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James T.","family":"Topham","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC Vancouver General Hospital Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassia","family":"Warren","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC Vancouver General Hospital Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Li","family":"Wong","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC Vancouver General Hospital Vancouver British Columbia Canada"},{"name":"Department of Medical Oncology British Columbia Cancer Agency Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael Kuan\u2010Ching","family":"Lee","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC Vancouver General Hospital Vancouver British Columbia Canada"},{"name":"Department of Medical Oncology British Columbia Cancer Agency Vancouver British Columbia Canada"},{"name":"Department of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Renouf","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC Vancouver General Hospital Vancouver British Columbia Canada"},{"name":"Department of Medical Oncology British Columbia Cancer Agency Vancouver British Columbia Canada"},{"name":"Department of Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David F.","family":"Schaeffer","sequence":"additional","affiliation":[{"name":"Pancreas Centre BC Vancouver General Hospital Vancouver British Columbia Canada"},{"name":"Department of Pathology and Laboratory Medicine University of British Columbia Vancouver British Columbia Canada"},{"name":"Division of Anatomical Pathology Vancouver General Hospital Vancouver British Columbia Canada"},{"name":"Genetic Pathology Evaluation Centre University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0155"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3398"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16965"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2344"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz181"},{"key":"e_1_2_9_7_1","unstructured":"RasheedZA MatsuiW MaitraA.Pathology of pancreatic stroma in PDAC [Internet].2012.http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22876385"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.04.021"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.17.00121","article-title":"Stromal content is correlated with tissue site, contrast retention, and survival in pancreatic adenocarcinoma","volume":"2","author":"Torphy RJ","year":"2018","journal-title":"JCO Precis Oncol"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6770"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.08.033"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.07.8824"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-013-9439-3"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304369"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.85"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2536479100"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-1467"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0739-z"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1214\/aoms\/1177703732"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1176342503"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1963.10500845"},{"key":"e_1_2_9_22_1","volume-title":"Model Selection and Multimodel Inference: a Practical Information\u2010Theoretic Approach","author":"Burnham KP","year":"2002"},{"key":"e_1_2_9_23_1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1198\/jasa.2004.s339","article-title":"The elements of statistical learning: data mining, inference, and prediction","volume":"99","author":"Ruppert D","year":"2004","journal-title":"J Am Stat Assoc"},{"key":"e_1_2_9_24_1","unstructured":"Human Protein Atlas.Pathology Atlas\u2014Pancreatic Cancer KRT6A [Internet].2020https:\/\/www.proteinatlas.org\/ENSG00000205420-KRT6A\/pathology\/pancreatic+cancer#ihc. Accessed May 15 2020."},{"key":"e_1_2_9_25_1","unstructured":"Human Protein Atlas.Pathology Atlas\u2014Pancreatic Cancer CTSV [Internet].2020https:\/\/www.proteinatlas.org\/ENSG00000136943-CTSV\/pathology\/pancreatic+cancer. Accessed May 15 2020."},{"key":"e_1_2_9_26_1","unstructured":"Human Protein Atlas.Pathology Atlas\u2014Pancreatic Cancer LY6D [Internet].2020https:\/\/www.proteinatlas.org\/ENSG00000167656-LY6D\/pathology\/pancreatic+cancer. Accessed May 15 2020."},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072397"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc4027"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2019-205939"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/COC.0000000000000205"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13187-013-0603-9"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-3169"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.07.007"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2432"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.33304","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.33304","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.33304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T07:53:51Z","timestamp":1723622031000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.33304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,29]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,1,15]]}},"alternative-id":["10.1002\/ijc.33304"],"URL":"https:\/\/doi.org\/10.1002\/ijc.33304","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,29]]},"assertion":[{"value":"2020-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}