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Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome

2014-10-09Journal article Open access
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dc.contributor.authorCamilo, Vânia
dc.contributor.authorBarros, Rita
dc.contributor.authorCelestino, Ricardo
dc.contributor.authorCastro, Patrícia
dc.contributor.authorVieira, Joana
dc.contributor.authorTeixeira, Manuel
dc.contributor.authorCarneiro, Fatima
dc.contributor.authorPinho de Sousa, João
dc.contributor.authorDavid, Leonor
dc.contributor.authorAlmeida, Raquel
dc.date.accessioned2015-01-13T11:23:59Z
dc.date.available2015-01-13T11:23:59Z
dc.date.issued2014-10-09
dc.description.abstractBackground Gastric cancer remains a serious health concern worldwide. Patients would greatly benefit from the discovery of new biomarkers that predict outcome more accurately and allow better treatment and follow-up decisions. Here, we used a retrospective, observational study to assess the expression and prognostic value of the transcription factors SOX2 and CDX2 in gastric cancer. Methods SOX2, CDX2, MUC5AC and MUC2 expression were assessed in 201 gastric tumors by immunohistochemistry. SOX2 and CDX2 expression were crossed with clinicopathological and follow-up data to determine their impact on tumor behavior and outcome. Moreover, SOX2 locus copy number status was assessed by FISH (N = 21) and Copy Number Variation Assay (N = 62). Results SOX2 was expressed in 52% of the gastric tumors and was significantly associated with male gender, T stage and N stage. Moreover, SOX2 expression predicted poorer patient survival, and the combination with CDX2 defined two molecular phenotypes, SOX2+CDX2- versus SOX2-CDX2+, that predict the worst and the best long-term patients’ outcome. These profiles combined with clinicopathological parameters stratify the prognosis of patients with intestinal and expanding tumors and in those without signs of venous invasion. Finally, SOX2 locus copy number gains were found in 93% of the samples reaching the amplification threshold in 14% and significantly associating with protein expression. Conclusions We showed, for the first time, that SOX2 combined with CDX2 expression profile in gastric cancer segregate patients into different prognostic groups, complementing the clinicopathological information. We further demonstrate a molecular mechanism for SOX2 expression in a subset of gastric cancer cases.por
dc.description.sponsorshipThis work was supported by Project NORTE - 07-0124-FEDER-000024 co-financed by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), under Quadro de Referência Estratégico Nacional (QREN), by Fundo Europeu de Desenvolvimento Regional (FEDER). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT. V.C. and R.B. acknowledge FCT for financial support (grant numbers SFRH/BD/63300/2009 and SFRH/BPD/68276/2010, respectively).por
dc.identifier.citationCamilo, V., Barros, R., Celestino, R., Castro, P., Vieira, J., Teixeira, M., Carneiro, F., Pinho de Sousa, J., David, L., & Almeida, R. (2014). Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome. 14, 1–11. https://doi.org/10.1186/1471-2407-14-753
dc.identifier.doi10.1186/1471-2407-14-753
dc.identifier.urihttp://hdl.handle.net/10400.22/5390
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherDafne Solerapor
dc.relation.publisherversionhttp://www.biomedcentral.com/content/pdf/1471-2407-14-753.pdfpor
dc.subjectSOX2por
dc.subjectCDX2por
dc.subjectGastric cancerpor
dc.subjectPrognosispor
dc.subjectSurvivalpor
dc.titleImmunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcomepor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage11por
oaire.citation.startPage1por
oaire.citation.titleBMC Cancerpor
oaire.citation.volume14por
person.familyNameCelestino
person.givenNameRicardo
person.identifier154697
person.identifier.ciencia-id301A-7536-FFE2
person.identifier.orcid0000-0002-9605-6433
person.identifier.ridJ-6048-2013
person.identifier.scopus-author-id57195924601
rcaap.rightsopenAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublication46a9688a-c1bc-4e3d-a293-86f9b2c03058
relation.isAuthorOfPublication.latestForDiscovery46a9688a-c1bc-4e3d-a293-86f9b2c03058

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