{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T18:40:04Z","timestamp":1792435204514,"version":"4.5.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100004951","name":"Atat\u00fcrk \u00dcniversitesi","doi-asserted-by":"publisher","award":["2025"],"award-info":[{"award-number":["2025"]}],"id":[{"id":"10.13039\/501100004951","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Gastroenterol"],"DOI":"10.1186\/s12876-026-05259-6","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:34:15Z","timestamp":1790152455000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Coordinated upregulation of Hippo, NF-\u03baB and interferon pathway genes in pancreatic ductal adenocarcinoma: a retrospective tissue qRT-PCR profiling study with external tumour-versus-non-tumour validation, molecular subtype and survival analyses"],"prefix":"10.1186","volume":"26","author":[{"given":"Eda","family":"Balkan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"K\u0131z\u0131lkaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevilay","family":"\u00d6zmen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Necip","family":"Altunda\u015f","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mert","family":"Y\u00fcksel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmut","family":"Akt\u00fcrk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulkadir","family":"Aktepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurhak","family":"Aksungur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"issue":"1","key":"5259_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","volume":"74","author":"RL Siegel","year":"2024","unstructured":"Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12\u201349. https:\/\/doi.org\/10.3322\/caac.21820.","journal-title":"CA Cancer J Clin"},{"issue":"4","key":"5259_CR2","doi-asserted-by":"publisher","first-page":"e214708","DOI":"10.1001\/jamanetworkopen.2021.4708","volume":"4","author":"L Rahib","year":"2021","unstructured":"Rahib L, Wehner MR, Matrisian LM, Nead KT. Estimated projection of US cancer incidence and death to 2040. JAMA Netw Open. 2021;4(4):e214708. https:\/\/doi.org\/10.1001\/jamanetworkopen.2021.4708.","journal-title":"JAMA Netw Open"},{"issue":"10242","key":"5259_CR3","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1016\/S0140-6736(20)30974-0","volume":"395","author":"JD Mizrahi","year":"2020","unstructured":"Mizrahi JD, Surana R, Valle JW, Shroff RT. Pancreatic cancer. Lancet. 2020;395(10242):2008\u201320. https:\/\/doi.org\/10.1016\/S0140-6736(20)30974-0.","journal-title":"Lancet"},{"issue":"8","key":"5259_CR4","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/s41575-020-0300-1","volume":"17","author":"AN Hosein","year":"2020","unstructured":"Hosein AN, Brekken RA, Maitra A. Pancreatic cancer stroma: an update on therapeutic targeting strategies. Nat Rev Gastroenterol Hepatol. 2020;17(8):487\u2013505. https:\/\/doi.org\/10.1038\/s41575-020-0300-1.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"11","key":"5259_CR5","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.annonc.2023.08.009","volume":"34","author":"T Conroy","year":"2023","unstructured":"Conroy T, Pfeiffer P, Vilgrain V, et al. Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(11):987\u20131002. https:\/\/doi.org\/10.1016\/j.annonc.2023.08.009.","journal-title":"Ann Oncol"},{"key":"5259_CR6","unstructured":"T.C. Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131, Halk Sa\u011fl\u0131\u011f\u0131 Genel M\u00fcd\u00fcrl\u00fc\u011f\u00fc, Kanser Dairesi Ba\u015fkanl\u0131\u011f\u0131. T\u00fcrkiye Kanser \u0130statistikleri 2020 [Turkish Cancer Statistics 2020]. Ankara: Ministry of Health of T\u00fcrkiye; 2020. https:\/\/hsgm.saglik.gov.tr\/depo\/birimler\/kanser-db\/Dokumanlar\/Istatistikler\/Turkiye_Kanser_Istatistikleri_2020.pdf."},{"issue":"6","key":"5259_CR7","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.ccell.2016.05.005","volume":"29","author":"F Zanconato","year":"2016","unstructured":"Zanconato F, Cordenonsi M, Piccolo S. YAP\/TAZ at the roots of cancer. Cancer Cell. 2016;29(6):783\u2013803. https:\/\/doi.org\/10.1016\/j.ccell.2016.05.005.","journal-title":"Cancer Cell"},{"issue":"6","key":"5259_CR8","doi-asserted-by":"publisher","first-page":"3317","DOI":"10.21873\/anticanres.13474","volume":"39","author":"D Ansari","year":"2019","unstructured":"Ansari D, Ohlsson H, Althini C, et al. The Hippo signaling pathway in pancreatic cancer. Anticancer Res. 2019;39(6):3317\u201321. https:\/\/doi.org\/10.21873\/anticanres.13474.","journal-title":"Anticancer Res"},{"issue":"18","key":"5259_CR9","doi-asserted-by":"publisher","first-page":"4510","DOI":"10.3390\/cancers13184510","volume":"13","author":"J Silke","year":"2021","unstructured":"Silke J, O\u2019Reilly LA. NF-\u03baB and pancreatic cancer; chapter and verse. Cancers (Basel). 2021;13(18):4510. https:\/\/doi.org\/10.3390\/cancers13184510.","journal-title":"Cancers (Basel)"},{"issue":"3","key":"5259_CR10","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1042\/BJ20140444","volume":"461","author":"J Zhang","year":"2014","unstructured":"Zhang J, Clark K, Lawrence T, Peggie MW, Cohen P. An unexpected twist to the activation of IKK\u03b2: TAK1 primes IKK\u03b2 for activation by autophosphorylation. Biochem J. 2014;461(3):531\u20137. https:\/\/doi.org\/10.1042\/BJ20140444.","journal-title":"Biochem J"},{"key":"5259_CR11","doi-asserted-by":"publisher","unstructured":"Muthalagu N, Monteverde T, Raffo-Iraolagoitia X, et al. Repression of the type I interferon pathway underlies MYC- and KRAS-dependent evasion of NK and B cells in pancreatic ductal adenocarcinoma. Cancer Discov. 2020;10(6):872\u201387. https:\/\/doi.org\/10.1158\/2159-8290.CD-19-0620.","DOI":"10.1158\/2159-8290.CD-19-0620"},{"key":"5259_CR12","doi-asserted-by":"publisher","unstructured":"Zhang Q, Meng F, Chen S, et al. Hippo signalling governs cytosolic nucleic acid sensing through YAP\/TAZ-mediated TBK1 blockade. Nat Cell Biol. 2017;19(4):362\u201374. https:\/\/doi.org\/10.1038\/ncb3496.","DOI":"10.1038\/ncb3496"},{"issue":"7541","key":"5259_CR13","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature14228","volume":"519","author":"K Taniguchi","year":"2015","unstructured":"Taniguchi K, Wu LW, Grivennikov SI, et al. A gp130\u2013Src\u2013YAP module links inflammation to epithelial regeneration. Nature. 2015;519(7541):57\u201362. https:\/\/doi.org\/10.1038\/nature14228.","journal-title":"Nature"},{"key":"5259_CR14","doi-asserted-by":"publisher","unstructured":"Gao Y, Yang Y, Yuan F, et al. TNF\u03b1-YAP\/p65-HK2 axis mediates breast cancer cell migration. Oncogenesis. 2017;6(9):e383. https:\/\/doi.org\/10.1038\/oncsis.2017.83.","DOI":"10.1038\/oncsis.2017.83"},{"issue":"24","key":"5259_CR15","doi-asserted-by":"publisher","first-page":"7309","DOI":"10.1158\/0008-5472.CAN-14-1354","volume":"74","author":"B Sainz Jr","year":"2014","unstructured":"Sainz B Jr, Mart\u00edn B, Tatari M, et al. ISG15 is a critical microenvironmental factor for pancreatic cancer stem cells. Cancer Res. 2014;74(24):7309\u201320. https:\/\/doi.org\/10.1158\/0008-5472.CAN-14-1354.","journal-title":"Cancer Res"},{"issue":"4","key":"5259_CR16","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","volume":"55","author":"SA Bustin","year":"2009","unstructured":"Bustin SA, Benes V, Garson JA, et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 2009;55(4):611\u201322. https:\/\/doi.org\/10.1373\/clinchem.2008.112797.","journal-title":"Clin Chem"},{"issue":"4","key":"5259_CR17","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2013\u2206\u2206C(T)) method. Methods. 2001;25(4):402\u20138. https:\/\/doi.org\/10.1006\/meth.2001.1262.","journal-title":"Methods"},{"issue":"3","key":"5259_CR18","doi-asserted-by":"publisher","first-page":"837","DOI":"10.2307\/2531595","volume":"44","author":"ER DeLong","year":"1988","unstructured":"DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837\u201345.","journal-title":"Biometrics"},{"key":"5259_CR19","unstructured":"Gene Expression Omnibus accession GSE62452. Microarray gene-expression profiles of 69 pancreatic tumors and 61 adjacent non-tumor tissues from patients with pancreatic ductal adenocarcinoma. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE62452."},{"issue":"10","key":"5259_CR20","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1038\/ng.3398","volume":"47","author":"RA Moffitt","year":"2015","unstructured":"Moffitt RA, Marayati R, Flate EL, et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. 2015;47(10):1168\u201378. https:\/\/doi.org\/10.1038\/ng.3398.","journal-title":"Nat Genet"},{"issue":"15","key":"5259_CR21","doi-asserted-by":"publisher","first-page":"e23867","DOI":"10.1096\/fj.202302484RR","volume":"38","author":"Q Chen","year":"2024","unstructured":"Chen Q, Chen Z, Zhang J, Cai Y, Wu S, He D, Cheng K, Gu X, Cai Y, Wang X, Li Y, Zhang M, Wu Z, Peng B. Dual and triple gene combinations of KRT5, KRT17, and S100A2 identify basal-like subtype of pancreatic ductal adenocarcinoma and correlate with survival outcome. FASEB J. 2024;38(15):e23867. https:\/\/doi.org\/10.1096\/fj.202302484RR.","journal-title":"FASEB J"},{"issue":"6","key":"5259_CR22","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/ncb2756","volume":"15","author":"F Calvo","year":"2013","unstructured":"Calvo F, Ege N, Grande-Garcia A, et al. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat Cell Biol. 2013;15(6):637\u201346. https:\/\/doi.org\/10.1038\/ncb2756.","journal-title":"Nat Cell Biol"},{"key":"5259_CR23","doi-asserted-by":"publisher","unstructured":"Aksungur N, K\u0131z\u0131lkaya M, Altunda\u015f N, et al. Molecular crosstalk between SIRT1, Wnt\/\u03b2-catenin signaling, and inflammatory pathways in renal transplant rejection: role of miRNAs, lncRNAs, IL-1, IL-6, and tubulointerstitial inflammation. Medicina (Kaunas). 2025;61(6):1073. https:\/\/doi.org\/10.3390\/medicina61061073.","DOI":"10.3390\/medicina61061073"},{"key":"5259_CR24","doi-asserted-by":"publisher","unstructured":"Altunda\u015f N, Balkan E, K\u0131z\u0131lkaya M, et al. Dickkopf-1 and cytoskeletal protein 4 mRNA expression associated with liver and kidney transplant rejection: prospective observational study. Medicine (Baltimore). 2025;104(36):e44271. https:\/\/doi.org\/10.1097\/MD.0000000000044271.","DOI":"10.1097\/MD.0000000000044271"},{"issue":"9","key":"5259_CR25","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1084\/jem.20111706","volume":"209","author":"A Ochi","year":"2012","unstructured":"Ochi A, Nguyen AH, Bedrosian AS, et al. MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells. J Exp Med. 2012;209(9):1671\u201387. https:\/\/doi.org\/10.1084\/jem.20111706.","journal-title":"J Exp Med"},{"key":"5259_CR26","doi-asserted-by":"publisher","unstructured":"Benci JL, Xu B, Qiu Y, et al. Tumor interferon signaling regulates a multigenic resistance program to immune checkpoint blockade. Cell. 2016;167(6):1540\u201354.e12. https:\/\/doi.org\/10.1016\/j.cell.2016.11.022.","DOI":"10.1016\/j.cell.2016.11.022"},{"key":"5259_CR27","doi-asserted-by":"publisher","unstructured":"Weill L, Shestakova E, Bonnefoy E. Transcription factor YY1 binds to the murine beta interferon promoter and regulates its transcriptional capacity with a dual activator\/repressor role. J Virol. 2003;77(5):2903\u201314. https:\/\/doi.org\/10.1128\/JVI.77.5.2903-2914.2003.","DOI":"10.1128\/JVI.77.5.2903-2914.2003"},{"key":"5259_CR28","doi-asserted-by":"publisher","unstructured":"Lau LF. CCN1\/CYR61: the very model of a modern matricellular protein. Cell Mol Life Sci. 2011;68(19):3149\u201363. https:\/\/doi.org\/10.1007\/s00018-011-0778-3.","DOI":"10.1007\/s00018-011-0778-3"},{"key":"5259_CR29","doi-asserted-by":"publisher","unstructured":"Charrier A, Brigstock DR. Regulation of pancreatic function by connective tissue growth factor (CTGF, CCN2). Cytokine Growth Factor Rev. 2013;24(1):59\u201368. https:\/\/doi.org\/10.1016\/j.cytogfr.2012.07.001.","DOI":"10.1016\/j.cytogfr.2012.07.001"},{"key":"5259_CR30","doi-asserted-by":"publisher","unstructured":"Altunda\u015f N, Balkan E, K\u0131z\u0131lkaya M, et al. The clinical role of SIRT-3 in the acute rejection process of kidney transplantation and its effects on graft outcomes: evaluation of biomarker potential. Medicina (Kaunas). 2025;61(3):457. https:\/\/doi.org\/10.3390\/medicina61030457.","DOI":"10.3390\/medicina61030457"},{"key":"5259_CR31","doi-asserted-by":"publisher","unstructured":"Deng Y, Lu J, Li W, et al. Reciprocal inhibition of YAP\/TAZ and NF-\u03baB regulates osteoarthritic cartilage degradation. Nat Commun. 2018;9(1):4564. https:\/\/doi.org\/10.1038\/s41467-018-07022-2.","DOI":"10.1038\/s41467-018-07022-2"},{"issue":"2","key":"5259_CR32","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/s00432-020-03427-z","volume":"147","author":"R Drexler","year":"2021","unstructured":"Drexler R, K\u00fcchler M, Wagner KC, Reese T, Feyerabend B, Kleine M, Oldhafer KJ. The clinical relevance of the Hippo pathway in pancreatic ductal adenocarcinoma. J Cancer Res Clin Oncol. 2021;147(2):373\u201391. https:\/\/doi.org\/10.1007\/s00432-020-03427-z.","journal-title":"J Cancer Res Clin Oncol"},{"issue":"21","key":"5259_CR33","doi-asserted-by":"publisher","first-page":"e130811","DOI":"10.1172\/jci.insight.130811","volume":"4","author":"B Tu","year":"2019","unstructured":"Tu B, Yao J, Ferri-Borgogno S, et al. YAP1 oncogene is a context-specific driver for pancreatic ductal adenocarcinoma. JCI Insight. 2019;4(21):e130811. https:\/\/doi.org\/10.1172\/jci.insight.130811.","journal-title":"JCI Insight"},{"issue":"3","key":"5259_CR34","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3892\/ijo.2026.5848","volume":"68","author":"S Rauschenberg","year":"2026","unstructured":"Rauschenberg S, Orgler-Gasche E, Karakas Zeybek D, Regel I, L\u00f6hr JM, \u00d6hlund D, G\u00fcnther M, Aguilera Munoz L. Unveiling sex differences in pancreatic ductal adenocarcinoma: current evidence and future directions (Review). Int J Oncol. 2026;68(3):35. https:\/\/doi.org\/10.3892\/ijo.2026.5848.","journal-title":"Int J Oncol"}],"container-title":["BMC Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12876-026-05259-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-026-05259-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-026-05259-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T18:02:41Z","timestamp":1792432961000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12876-026-05259-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5259"],"URL":"https:\/\/doi.org\/10.1186\/s12876-026-05259-6","relation":{},"ISSN":["1471-230X"],"issn-type":[{"value":"1471-230X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]},"assertion":[{"value":"31 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Atat\u00fcrk University Faculty of Medicine Clinical Research Ethics Committee (approval code: B30.2 ATA-0.01.00\/112\/2026).Written informed consent was obtained from all individual participants included in the study or from their legal representatives.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declaration"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declaration"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declaration"}}],"article-number":"666"}}