{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T10:52:22Z","timestamp":1774003942344,"version":"3.50.1"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016218","name":"Regional Agency for the Development of Research Technology and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016218","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/00006\/2025"],"award-info":[{"award-number":["UID\/00006\/2025"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/PRR\/00006\/2025"],"award-info":[{"award-number":["UID\/PRR\/00006\/2025"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Treatment and Research Communications"],"published-print":{"date-parts":[[2026]]},"DOI":"10.1016\/j.ctarc.2025.101091","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T16:52:40Z","timestamp":1767372760000},"page":"101091","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Prognostic role and clinicopathological features of SMAD4 gene mutation in pancreatic cancer: a systematic review and meta-analysis"],"prefix":"10.1016","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5550-069X","authenticated-orcid":false,"given":"T\u00e2nia","family":"Rodrigues","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joana","family":"Albuquerque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joana","family":"Cardoso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivo","family":"Sousa-Ferreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Paulo","family":"Martins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Lu\u00eds Passos","family":"Coelho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ctarc.2025.101091_bib0001","article-title":"Glob cancer Obs cancer today pancreas","year":"2022","journal-title":"Globocan"},{"issue":"77","key":"10.1016\/j.ctarc.2025.101091_bib0002","first-page":"10","article-title":"American Cancer Society. 2023","year":"2023","journal-title":"Cancer Facts Fig."},{"issue":"1","key":"10.1016\/j.ctarc.2025.101091_bib0003","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"issue":"11","key":"10.1016\/j.ctarc.2025.101091_bib0004","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.annonc.2023.08.009","article-title":"Pancreatic cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up\u2606","volume":"34","author":"Conroy","year":"2023","journal-title":"Ann. Oncol."},{"issue":"8","key":"10.1016\/j.ctarc.2025.101091_bib0005","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/j.cell.2023.02.014","article-title":"Pancreatic cancer: advances and challenges","volume":"186","author":"Halbrook","year":"2023","journal-title":"Cell"},{"issue":"5","key":"10.1016\/j.ctarc.2025.101091_bib0006","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.molcel.2004.07.016","article-title":"Structural basis of heteromeric Smad protein assembly in TGF-\u03b2 signaling","volume":"15","author":"Chacko","year":"2004","journal-title":"Mol. Cell"},{"issue":"5247","key":"10.1016\/j.ctarc.2025.101091_bib0007","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1126\/science.271.5247.350","article-title":"DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1","volume":"271","author":"Hahn","year":"1996","journal-title":"Science"},{"issue":"12","key":"10.1016\/j.ctarc.2025.101091_bib0008","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1038\/bjc.1998.731","article-title":"Smad4 (DPC4)\u2013a potent tumour suppressor?","volume":"78","author":"Duff","year":"1998","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.ctarc.2025.101091_bib0009","article-title":"Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression","author":"Wilentz","year":"2000","journal-title":"Cancer Res."},{"issue":"2","key":"10.1016\/j.ctarc.2025.101091_bib0010","doi-asserted-by":"crossref","DOI":"10.1016\/j.ccell.2017.07.007","article-title":"Integrated genomic characterization of pancreatic ductal adenocarcinoma","volume":"32","author":"Raphael","year":"2017","journal-title":"Cancer Cell"},{"issue":"10","key":"10.1016\/j.ctarc.2025.101091_bib0011","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21103534","article-title":"SMAD4 and the tgf\u03b2 pathway in patients with pancreatic ductal adenocarcinoma","volume":"21","author":"Dardare","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"10","key":"10.1016\/j.ctarc.2025.101091_bib0012","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0110182","article-title":"Meta-analysis of the prognostic value of Smad4 immunohistochemistry in various cancers","volume":"9","author":"Du","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.ctarc.2025.101091_bib0013","first-page":"1","article-title":"Prognostic value of SMAD4 in pancreatic cancer: a meta-analysis","volume":"9","author":"Xing","year":"2016","journal-title":"Transl. Oncol."},{"key":"10.1016\/j.ctarc.2025.101091_bib0014","first-page":"16704","article-title":"Clinicopathological significance of SMAD4 loss in pancreatic ductal adenocarcinomas: a systematic review and meta-analysis","volume":"8","author":"Wang","year":"2017","journal-title":"Impact J., LLC"},{"issue":"12","key":"10.1016\/j.ctarc.2025.101091_bib0015","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1089\/gtmb.2020.0078","article-title":"Clinical effect of driver mutations of KRAS, CDKN2A\/P16, TP53, and SMAD4 in pancreatic cancer: a meta-analysis","volume":"24","author":"Gu","year":"2020","journal-title":"Genet. Test. Mol. Biomarkers"},{"issue":"23","key":"10.1016\/j.ctarc.2025.101091_bib0016","doi-asserted-by":"crossref","first-page":"4531","DOI":"10.1200\/JCO.2002.12.063","article-title":"DPC4\/Smad4 expression and outcome in pancreatic ductal adenocarcinoma","volume":"20","author":"Biankin","year":"2002","journal-title":"J. Clin. Oncol."},{"issue":"12","key":"10.1016\/j.ctarc.2025.101091_bib0017","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.3748\/wjg.v9.i12.2764","article-title":"Loss of DPC4 expression and its correlation with clinicopathological parameters in pancreatic carcinoma","volume":"9","author":"Hua","year":"2003","journal-title":"World J. Gastroenterol."},{"issue":"2","key":"10.1016\/j.ctarc.2025.101091_bib0018","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1097\/SLA.0b013e3182827a65","article-title":"Immunohistochemically detected expression of 3 major genes (CDKN2A\/p16, TP53, and SMAD4\/DPC4) strongly predicts survival in patients with resectable pancreatic cancer","volume":"258","author":"Oshima","year":"2013","journal-title":"Ann. Surg."},{"issue":"2","key":"10.1016\/j.ctarc.2025.101091_bib0019","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s13402-012-0072-x","article-title":"Multivariate analysis of immunohistochemical evaluation of protein expression in pancreatic ductal adenocarcinoma reveals prognostic significance for persistent Smad4 expression only","volume":"35","author":"Ottenhof","year":"2012","journal-title":"Cell Oncol. (Dordr)"},{"issue":"12","key":"10.1016\/j.ctarc.2025.101091_bib0020","first-page":"4115","article-title":"The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma","volume":"7","author":"Tascilar","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ctarc.2025.101091_bib0021","first-page":"1173","article-title":"The dissociated expression of protein and messenger RNA of DPC4 in human invasive ductal carcinoma of the pancreas and their implication for patient outcome","volume":"24","author":"Toga","year":"2004","journal-title":"Anticancer Res."},{"issue":"9","key":"10.1016\/j.ctarc.2025.101091_bib0022","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1002\/bjs.10187","article-title":"Infiltrating immune cells and gene mutations in pancreatic ductal adenocarcinoma","volume":"103","author":"Wang","year":"2016","journal-title":"Br. J. Surg."},{"issue":"2","key":"10.1016\/j.ctarc.2025.101091_bib0023","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1097\/MPA.0b013e31825b6ab0","article-title":"Genetic alterations of K-ras, p53, c-erbB-2, and DPC4 in pancreatic ductal adenocarcinoma and their correlation with patient survival","volume":"42","author":"Shin","year":"2013","journal-title":"Pancreas."},{"issue":"1","key":"10.1016\/j.ctarc.2025.101091_bib0024","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2288-12-9","article-title":"Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves","volume":"12","author":"Guyot","year":"2012","journal-title":"BMC. Med. Res. Methodol."},{"key":"10.1016\/j.ctarc.2025.101091_bib0025","first-page":"1","article-title":"Survival analysis for health economic evaluation and cost-effectiveness modeling","volume":"95","author":"Survhe","year":"2020","journal-title":"J. Stat. Softw."},{"key":"10.1016\/j.ctarc.2025.101091_bib0026","unstructured":"Therneau T. A package for survival analysis in R; version 3.2-11. 2021.https:\/\/CRAN.R-project.org\/package=survival."},{"key":"10.1016\/j.ctarc.2025.101091_bib0027","unstructured":"Cochrane Library. Risk of bias in non-randomized studies.; 2021."},{"issue":"23","key":"10.1016\/j.ctarc.2025.101091_bib0028","article-title":"The trim-and-fill method for publication bias: practical guidelines and recommendations based on a large database of meta-analyses","volume":"98","author":"Shi","year":"2019","journal-title":"Med (United States)"},{"issue":"6","key":"10.1016\/j.ctarc.2025.101091_bib0029","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1309\/WF03-NFCE-7BRH-7C26","article-title":"Immunohistochemical labeling for the Dpc4 gene product is a specific marker for adenocarcinoma in biopsy specimens of the pancreas and bile duct","volume":"116","author":"Tascilar","year":"2001","journal-title":"Am. J. Clin. Pathol."},{"issue":"14","key":"10.1016\/j.ctarc.2025.101091_bib0030","doi-asserted-by":"crossref","first-page":"4674","DOI":"10.1158\/1078-0432.CCR-09-0227","article-title":"SMAD4 Gene mutations are associated with poor prognosis in pancreatic cancer","volume":"15","author":"Blackford","year":"2009","journal-title":"Clin. Cancer Res."},{"issue":"7","key":"10.1016\/j.ctarc.2025.101091_bib0031","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1038\/bjc.2013.486","article-title":"Reduced expression of bone morphogenetic protein receptor IA in pancreatic cancer is associated with a poor prognosis","volume":"109","author":"Voorneveld","year":"2013","journal-title":"Br. J. Cancer"},{"issue":"10","key":"10.1016\/j.ctarc.2025.101091_bib0032","article-title":"Integration of bioinformatics resources reveals the therapeutic benefits of gemcitabine and cell cycle intervention in SMAD4-deleted pancreatic ductal adenocarcinoma","volume":"10","author":"Hsieh","year":"2019","journal-title":"Genes(Basel)"},{"issue":"5","key":"10.1016\/j.ctarc.2025.101091_bib0033","doi-asserted-by":"crossref","DOI":"10.3390\/jcm9051250","article-title":"Multiparametric modelling of survival in pancreatic ductal adenocarcinoma using clinical, histomorphological, genetic and image-derived parameters","volume":"9","author":"Kaissis","year":"2020","journal-title":"J. Clin. Med."},{"issue":"14","key":"10.1016\/j.ctarc.2025.101091_bib0034","doi-asserted-by":"crossref","first-page":"3732","DOI":"10.1158\/1078-0432.CCR-19-3034","article-title":"TP53 Mutations predict sensitivity to adjuvant gemcitabine in patients with pancreatic ductal adenocarcinoma: next-generation sequencing results from the CONKO-001 trial","volume":"26","author":"Sinn","year":"2020","journal-title":"Clin. Cancer Res."},{"issue":"6","key":"10.1016\/j.ctarc.2025.101091_bib0035","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1111\/cas.14425","article-title":"Combination of KRAS and SMAD4 mutations in formalin-fixed paraffin-embedded tissues as a biomarker for pancreatic cancer","volume":"111","author":"Yokose","year":"2020","journal-title":"Cancer Sci."},{"key":"10.1016\/j.ctarc.2025.101091_bib0036","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2021.103327","article-title":"A genetically defined signature of responsiveness to erlotinib in early-stage pancreatic cancer patients: results from the CONKO-005 trial","volume":"66","author":"Hoyer","year":"2021","journal-title":"EBioMedicine"},{"issue":"6","key":"10.1016\/j.ctarc.2025.101091_bib0037","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1093\/ajcp\/101.6.684","article-title":"Overexpression of p53 protein in adenocarcinoma of the pancreas","volume":"101","author":"DiGiuseppe","year":"1994","journal-title":"Am. J. Clin. Pathol."},{"issue":"2","key":"10.1016\/j.ctarc.2025.101091_bib0038","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0046-8177(99)90265-4","article-title":"Immunohistochemical evaluation of K-ras, p53, and HER-2\/neu expression in hyperplastic, dysplastic, and carcinomatous lesions of the pancreas: evidence for multistep carcinogenesis","volume":"30","author":"Apple","year":"1999","journal-title":"Hum. Pathol."},{"issue":"7","key":"10.1016\/j.ctarc.2025.101091_bib0039","first-page":"2002","article-title":"Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression","volume":"60","author":"Wilentz","year":"2000","journal-title":"Cancer Res."},{"issue":"3","key":"10.1016\/j.ctarc.2025.101091_bib0040","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1007\/s00534-012-0518-6","article-title":"Tumoral epithelial and stromal expression of SMAD proteins in pancreatic ductal adenocarcinomas","volume":"20","author":"Handra-Luca","year":"2013","journal-title":"J. Hepatobiliary. Pancreat. Sci."},{"issue":"9","key":"10.1016\/j.ctarc.2025.101091_bib0041","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1093\/annonc\/mdr617","article-title":"Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma","volume":"23","author":"Bachet","year":"2012","journal-title":"Ann. Oncol."},{"issue":"12","key":"10.1016\/j.ctarc.2025.101091_bib0042","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.3748\/wjg.v9.i12.2764","article-title":"Loss of DPC4 expression and its correlation with clinicopathological parameters in pancreatic carcinoma","volume":"9","author":"Hua","year":"2003","journal-title":"World J. Gastroenterol."},{"issue":"2","key":"10.1016\/j.ctarc.2025.101091_bib0043","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1097\/SLA.0b013e3182827a65","article-title":"Immunohistochemically detected expression of 3 major genes (CDKN2A\/p16, TP53, and SMAD4\/DPC4) strongly predicts survival in patients with resectable pancreatic cancer","volume":"258","author":"Oshima","year":"2013","journal-title":"Ann. Surg."},{"issue":"1","key":"10.1016\/j.ctarc.2025.101091_bib0044","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0262439","article-title":"Pancreatic ductal adenocarcinoma: prognostic indicators of advanced disease","volume":"17","author":"Kruger","year":"2022","journal-title":"PLoS. One"},{"issue":"10","key":"10.1016\/j.ctarc.2025.101091_bib0045","doi-asserted-by":"crossref","first-page":"3316","DOI":"10.1158\/1078-0432.CCR-10-3284","article-title":"Tissue biomarkers for prognosis in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis","volume":"17","author":"Jamieson","year":"2011","journal-title":"Clin. Cancer Res."}],"container-title":["Cancer Treatment and Research Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2468294225002266?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2468294225002266?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T08:37:43Z","timestamp":1773995863000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2468294225002266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":45,"alternative-id":["S2468294225002266"],"URL":"https:\/\/doi.org\/10.1016\/j.ctarc.2025.101091","relation":{},"ISSN":["2468-2942"],"issn-type":[{"value":"2468-2942","type":"print"}],"subject":[],"published":{"date-parts":[[2026]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Prognostic role and clinicopathological features of SMAD4 gene mutation in pancreatic cancer: a systematic review and meta-analysis","name":"articletitle","label":"Article Title"},{"value":"Cancer Treatment and Research Communications","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ctarc.2025.101091","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"101091"}}