{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:38:38Z","timestamp":1787236718847,"version":"build-2736575974"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005199","name":"Chinese Medicine Research Program of Zhejiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Despite improvements reported in diagnosis and treatments in recent decades, pancreatic cancer is still characterized by poor prognosis and low survival rate among solid tumors. Intensive interests have grown in exploring novel predictive biomarkers, aiming to enhance the efficiency in early detection and treatment prognosis. In this study, we identified the differentially expressed genes (DEGs) in pancreatic cancer by analyzing five gene expression profiles and established the functional modules according to the functional interaction (FI) network between the DEGs. A significant upregulation of the selected DEG, interferon (IFN)-induced transmembrane protein 1 (IFITM1), was evaluated in several bioinformatics online tools and verified with immunohistochemistry staining from samples of 90 patients with pancreatic cancer. Prognostic data showed that high expression of IFITM1 associated with poor survival, and multivariate Cox regression analysis showed IFITM1 was one of the independent prognostic factors for overall survival. Meanwhile, significant correlations of the expression of IFITM1 and the infiltration of immune cells were found by TIMER. Furthermore, a higher level of IFITM1 was assessed in pancreatic cancer cell lines compared to normal human pancreatic duct epithelial cells, and silencing IFITM1 in tumor cells remarkedly inhibited cancer tumorigenicity. Collectively, our findings suggested that IFITM1 might have promising utility for pancreatic cancer.<\/jats:p>","DOI":"10.3389\/fonc.2021.626883","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T03:03:43Z","timestamp":1616382223000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of IFN-Induced Transmembrane Protein 1 With Prognostic Value in Pancreatic Cancer Using Network Module-Based Analysis"],"prefix":"10.3389","volume":"11","author":[{"given":"Lingyun","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinli","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danfang","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiyuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senxiang","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2913","DOI":"10.1158\/0008-5472.CAN-14-0155","article-title":"Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States","volume":"74","author":"Rahib","year":"2014","journal-title":"Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41416-020-0863-1","article-title":"Molecular profiling of stroma highlights stratifin as a novel biomarker of poor prognosis in pancreatic ductal adenocarcinoma","volume":"123","author":"Robin","year":"2020","journal-title":"Br J Cancer"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e135","DOI":"10.1016\/S1470-2045(19)30795-8","article-title":"Current and emerging therapies for patients with advanced pancreatic ductal adenocarcinoma: a bright future","volume":"21","author":"Christenson","year":"2020","journal-title":"Lancet Oncol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/nri3344","article-title":"The broad-spectrum antiviral functions of IFIT and IFITM proteins","volume":"13","author":"Diamond","year":"2013","journal-title":"Nat Rev Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/0092-8674(84)90270-8","article-title":"Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells","volume":"38","author":"Friedman","year":"1984","journal-title":"Cell."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.3892\/or.2014.3110","article-title":"Aberrant DNA methylation in the IFITM1 promoter enhances the metastatic phenotype in an intraperitoneal xenograft model of human ovarian cancer","volume":"31","author":"Kim","year":"2014","journal-title":"Oncol Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.ajpath.2012.03.027","article-title":"Overexpression of IFITM1 has clinicopathologic effects on gastric cancer and is regulated by an epigenetic mechanism","volume":"181","author":"Lee","year":"2012","journal-title":"Am J Pathol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1002\/ijc.31926","article-title":"Interferon-induced transmembrane protein 1-mediated EGFR\/SOX2 signaling axis is essential for progression of non-small cell lung cancer","volume":"144","author":"Yang","year":"2019","journal-title":"Int J Cancer."},{"key":"B9","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.canlet.2015.07.034","article-title":"IFITM1 promotes the metastasis of human colorectal cancer via CAV-1","volume":"368","author":"Yu","year":"2015","journal-title":"Cancer Lett."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.7314\/APJCP.2016.17.4.2297","article-title":"Interferon induced transmembrane Protein-1 gene expression as a biomarker for early detection of invasive potential of oral squamous cell carcinomas","volume":"17","author":"Ramanathan","year":"2016","journal-title":"Asian Pac J Cancer Prev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"86039","DOI":"10.18632\/oncotarget.13325","article-title":"Interferon-induced transmembrane protein 1 (IFITM1) is required for the progression of colorectal cancer","volume":"7","author":"Sari","year":"2016","journal-title":"Oncotarget."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2448","DOI":"10.1093\/bioinformatics\/btg345","article-title":"A random variance model for detection of differential gene expression in small microarray experiments","volume":"19","author":"Wright","year":"2003","journal-title":"Bioinformatics."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.1002\/pmic.201400515","article-title":"FunRich: an open access standalone functional enrichment and interaction network analysis tool","volume":"15","author":"Pathan","year":"2015","journal-title":"Proteomics."},{"key":"B14","doi-asserted-by":"publisher","first-page":"BSR20180519","DOI":"10.1042\/BSR20180519","article-title":"Network pharmacology-based identification of major component of Angelica sinensis and its action mechanism for the treatment of acute myocardial infarction","volume":"38","author":"Niu","year":"2018","journal-title":"Biosci Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/ng0707-807","article-title":"On the design and analysis of gene expression studies in human populations","volume":"39","author":"Akey","year":"2007","journal-title":"Nat Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"D691","DOI":"10.1093\/nar\/gkq1018","article-title":"Reactome: a database of reactions, pathways and biological processes","volume":"39","author":"Croft","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"146","DOI":"10.12688\/f1000research.4431.2","article-title":"ReactomeFIViz: a Cytoscape app for pathway and network-based data analysis","volume":"3","author":"Wu","year":"2014","journal-title":"F1000Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"325","DOI":"10.3389\/fonc.2019.00325","article-title":"Identification of LIFR. PIK3R1, and MMP12 as novel prognostic signatures in gallbladder cancer using network-based module analysis","volume":"9","author":"Zhao","year":"2019","journal-title":"Front Oncol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. tissue-based map of the human proteome","volume":"347","author":"Uhlen","year":"2015","journal-title":"Science."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1476-5586(04)80047-2","article-title":"ONCOMINE: a cancer microarray database and integrated data-mining platform","volume":"6","author":"Rhodes","year":"2004","journal-title":"Neoplasia."},{"key":"B22","doi-asserted-by":"publisher","first-page":"W98","DOI":"10.1093\/nar\/gkx247","article-title":"GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses","volume":"45","author":"Tang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"267","DOI":"10.3389\/fcell.2019.00267","article-title":"The therapeutic potential of adipose tissue-derived mesenchymal stem cells to enhance radiotherapy effects on hepatocellular carcinoma","volume":"7","author":"Wu","year":"2019","journal-title":"Front Cell Dev Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"D767","DOI":"10.1093\/nar\/gkn892","article-title":"Human protein reference database\u22122009 update","volume":"37","author":"Keshava Prasad","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"D470","DOI":"10.1093\/nar\/gku1204","article-title":"The BioGRID interaction database: 2015 update","volume":"43","author":"Chatr-Aryamontri","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"R95","DOI":"10.1186\/gb-2007-8-5-r95","article-title":"Unequal evolutionary conservation of human protein interactions in interologous networks","volume":"8","author":"Brown","year":"2007","journal-title":"Genome Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"D358","DOI":"10.1093\/nar\/gkt1115","article-title":"The MIntAct project\u2013IntAct as a common curation platform for 11 molecular interaction databases","volume":"42","author":"Orchard","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"D857","DOI":"10.1093\/nar\/gkr930","article-title":"MINT, the molecular interaction database: 2012 update","volume":"40","author":"Licata","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"D449","DOI":"10.1093\/nar\/gkh086","article-title":"The database of interacting proteins: 2004 update","volume":"32","author":"Salwinski","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"R53","DOI":"10.1186\/gb-2010-11-5-r53","article-title":"A human functional protein interaction network and its application to cancer data analysis","volume":"11","author":"Wu","year":"2010","journal-title":"Genome Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"38","DOI":"10.15171\/mejdd.2018.126","article-title":"An increased level of aryl hydrocarbon receptor in patients with pancreatic cancer","volume":"11","author":"Masoudi","year":"2019","journal-title":"Middle East J Dig Dis."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3587","DOI":"10.1158\/1078-0432.CCR-04-1813","article-title":"Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia","volume":"11","author":"Segara","year":"2005","journal-title":"Clin Cancer Res."},{"key":"B33","first-page":"2016","article-title":"Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia","volume":"55","author":"Badea","year":"2008","journal-title":"Hepatogastroenterology."},{"key":"B34","first-page":"2649","article-title":"Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer","volume":"63","author":"Logsdon","year":"2003","journal-title":"Cancer Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1111\/j.1349-7006.2005.00064.x","article-title":"Experimental trial for diagnosis of pancreatic ductal carcinoma based on gene expression profiles of pancreatic ductal cells","volume":"96","author":"Ishikawa","year":"2005","journal-title":"Cancer Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/S0002-9440(10)63911-9","article-title":"Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays","volume":"162","author":"Iacobuzio-Donahue","year":"2003","journal-title":"Am J Pathol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"6626","DOI":"10.1038\/sj.onc.1208804","article-title":"Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions","volume":"24","author":"Buchholz","year":"2005","journal-title":"Oncogene."},{"key":"B38","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1593\/neo.04295","article-title":"Gene expression profiling of microdissected pancreatic ductal carcinomas using high-density DNA microarrays","volume":"6","author":"Grutzmann","year":"2004","journal-title":"Neoplasia."},{"key":"B39","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.ccr.2009.07.016","article-title":"FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt","volume":"16","author":"Pei","year":"2009","journal-title":"Cancer Cell."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1158\/0008-5472.CAN-05-2731","article-title":"Identification of the IFITM family as a new molecular marker in human colorectal tumors","volume":"66","author":"Andreu","year":"2006","journal-title":"Cancer Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"9085435","DOI":"10.1155\/2019\/9085435","article-title":"inhibiting of proliferation, migration, and invasion in lung cancer induced by silencing Interferon-Induced Transmembrane Protein 1 (IFITM1)","volume":"2019","author":"Yan","year":"2019","journal-title":"Biomed Res Int."},{"key":"B42","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s40364-016-0064-5","article-title":"Expression of IFITM1 as a prognostic biomarker in resected gastric and esophageal adenocarcinoma","volume":"4","author":"Borg","year":"2016","journal-title":"Biomark Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.canlet.2004.08.022","article-title":"The interferon-inducible 9-27 gene modulates the susceptibility to natural killer cells and the invasiveness of gastric cancer cells","volume":"221","author":"Yang","year":"2005","journal-title":"Cancer Lett."},{"key":"B44","doi-asserted-by":"publisher","first-page":"6097","DOI":"10.1158\/1078-0432.CCR-07-4761","article-title":"IFN-induced transmembrane protein 1 promotes invasion at early stage of head and neck cancer progression","volume":"14","author":"Hatano","year":"2008","journal-title":"Clin Cancer Res."},{"key":"B45","first-page":"16007","article-title":"Prognostic significance of INF-induced transmembrane protein 1 in colorectal cancer","volume":"8","author":"He","year":"2015","journal-title":"Int J Clin Exp Pathol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s12253-017-0314-3","article-title":"DDR2 and IFITM1 are prognostic markers in gallbladder squamous cell\/adenosquamous carcinomas and adenocarcinomas","volume":"25","author":"Li","year":"2019","journal-title":"Pathol Oncol Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.critrevonc.2019.02.010","article-title":"Matrix metalloproteinases participation in the metastatic process and their diagnostic and therapeutic applications in cancer","volume":"137","author":"Gonzalez-Avila","year":"2019","journal-title":"Crit Rev Oncol Hematol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s13058-014-0506-7","article-title":"Targeting interferon response genes sensitizes aromatase inhibitor resistant breast cancer cells to estrogen-induced cell death","volume":"17","author":"Choi","year":"2015","journal-title":"Breast Cancer Res."},{"key":"B49","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.canlet.2017.04.005","article-title":"IFITM1 suppression blocks proliferation and invasion of aromatase inhibitor-resistant breast cancer in vivo by JAK\/STAT-mediated induction of p21","volume":"399","author":"Lui","year":"2017","journal-title":"Cancer Lett."},{"key":"B50","doi-asserted-by":"publisher","first-page":"e91","DOI":"10.1038\/oncsis.2014.5","article-title":"A mesenchymal glioma stem cell profile is related to clinical outcome","volume":"3","author":"Balbous","year":"2014","journal-title":"Oncogenesis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s40291-020-00469-4","article-title":"Deciphering the roles of IFITM1 in tumors","volume":"24","author":"Liang","year":"2020","journal-title":"Mol Diagn Ther"},{"key":"B52","doi-asserted-by":"publisher","first-page":"3115","DOI":"10.1111\/cas.13640","article-title":"Combination of IFITM1 knockdown and radiotherapy inhibits the growth of oral cancer","volume":"109","author":"Yang","year":"2018","journal-title":"Cancer Sci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1093\/abbs\/gmp034","article-title":"Binding of IFITM1 enhances the inhibiting effect of caveolin-1 on ERK activation","volume":"41","author":"Xu","year":"2009","journal-title":"Acta Biochim Biophys Sin."},{"key":"B54","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1089\/jir.2010.0112","article-title":"The small interferon-induced transmembrane genes and proteins","volume":"31","author":"Siegrist","year":"2011","journal-title":"J Interferon Cytokine Res."}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.626883\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T03:03:47Z","timestamp":1616382227000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.626883\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":54,"alternative-id":["10.3389\/fonc.2021.626883"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2021.626883","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]},"article-number":"626883"}}