Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome
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 prog...
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| Veröffentlicht in: | BMC cancer 2014-10, Vol.14 (1), p.753-753, Article 753 |
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| creator | Camilo, Vânia Barros, Rita Celestino, Ricardo Castro, Patrícia Vieira, Joana Teixeira, Manuel R Carneiro, Fátima Pinto-de-Sousa, João David, Leonor Almeida, Raquel |
| description | 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.
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).
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.
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. |
| doi_str_mv | 10.1186/1471-2407-14-753 |
| format | Article |
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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).
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.
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.</description><identifier>ISSN: 1471-2407</identifier><identifier>EISSN: 1471-2407</identifier><identifier>DOI: 10.1186/1471-2407-14-753</identifier><identifier>PMID: 25300947</identifier><language>eng</language><publisher>England: BioMed Central</publisher><subject>Adenocarcinoma - genetics ; Adenocarcinoma - metabolism ; Adenocarcinoma - mortality ; Adenocarcinoma - surgery ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Cancer therapies ; CDX2 Transcription Factor ; Deoxyribonucleic acid ; DNA ; DNA Copy Number Variations ; Female ; Gastric cancer ; Gene Amplification ; Genetic testing ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Medical prognosis ; Middle Aged ; Pathology ; Phenotype ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; SOXB1 Transcription Factors - genetics ; SOXB1 Transcription Factors - metabolism ; Stomach Neoplasms - genetics ; Stomach Neoplasms - metabolism ; Stomach Neoplasms - mortality ; Stomach Neoplasms - surgery ; Studies ; Treatment Outcome ; Tumors ; Young Adult</subject><ispartof>BMC cancer, 2014-10, Vol.14 (1), p.753-753, Article 753</ispartof><rights>2014 Camilo et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Camilo et al.; licensee BioMed Central Ltd. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b512t-c94aac38ab38c7255ef17f592460daa63bc236c090ceaa18727f37462834e8cf3</citedby><cites>FETCH-LOGICAL-b512t-c94aac38ab38c7255ef17f592460daa63bc236c090ceaa18727f37462834e8cf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210532/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210532/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25300947$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Camilo, Vânia</creatorcontrib><creatorcontrib>Barros, Rita</creatorcontrib><creatorcontrib>Celestino, Ricardo</creatorcontrib><creatorcontrib>Castro, Patrícia</creatorcontrib><creatorcontrib>Vieira, Joana</creatorcontrib><creatorcontrib>Teixeira, Manuel R</creatorcontrib><creatorcontrib>Carneiro, Fátima</creatorcontrib><creatorcontrib>Pinto-de-Sousa, João</creatorcontrib><creatorcontrib>David, Leonor</creatorcontrib><creatorcontrib>Almeida, Raquel</creatorcontrib><title>Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome</title><title>BMC cancer</title><addtitle>BMC Cancer</addtitle><description>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.
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).
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.
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.</description><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - surgery</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cancer therapies</subject><subject>CDX2 Transcription Factor</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Copy Number Variations</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gene Amplification</subject><subject>Genetic testing</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Pathology</subject><subject>Phenotype</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Retrospective Studies</subject><subject>SOXB1 Transcription Factors - genetics</subject><subject>SOXB1 Transcription Factors - metabolism</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Stomach Neoplasms - mortality</subject><subject>Stomach Neoplasms - surgery</subject><subject>Studies</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>1471-2407</issn><issn>1471-2407</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp1kc1P3DAQxa0KBJRy76myxDnUX4mTSyW0tBQJiUOLxM2aTBzWKImD7SDx3-PV0hVI5eQnz_jnefMI-crZGed19Z0rzQuhmC64KnQpP5Gj3dXeG31IPsf4wBjXNasPyKEoJWON0kfEXY3jMvm1i8nj2o4OYaCjHywuAwQ6r-3k0_NsI_U9vYeYgkOKMKENtIVoO-on-ufmTlCYOrq6yGIOtnOY6AzJ2SlRvyT0o_1C9nsYoj15PY_J7a-ff1e_i-uby6vV-XXRllykAhsFgLKGVtaoRVnanuu-bISqWAdQyRaFrJA1DC0Ar7XQvdSqErVUtsZeHpMfW-68tKPtMI8QYDBzcCOEZ-PBmfeVya3NvX8ySnBWSpEBqy2gdf4DwPtKdmc2qzabVWdlchKZcvo6RvCPi43JPPglTNm54RXPVhvBq9zFtl0YfIzB9rtvODObiP8H_vbW3-7Bv0zlC9ubo1E</recordid><startdate>20141009</startdate><enddate>20141009</enddate><creator>Camilo, Vânia</creator><creator>Barros, Rita</creator><creator>Celestino, Ricardo</creator><creator>Castro, Patrícia</creator><creator>Vieira, Joana</creator><creator>Teixeira, Manuel R</creator><creator>Carneiro, Fátima</creator><creator>Pinto-de-Sousa, João</creator><creator>David, Leonor</creator><creator>Almeida, Raquel</creator><general>BioMed Central</general><general>BioMed Central Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20141009</creationdate><title>Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome</title><author>Camilo, Vânia ; Barros, Rita ; Celestino, Ricardo ; Castro, Patrícia ; Vieira, Joana ; Teixeira, Manuel R ; Carneiro, Fátima ; Pinto-de-Sousa, João ; David, Leonor ; Almeida, Raquel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b512t-c94aac38ab38c7255ef17f592460daa63bc236c090ceaa18727f37462834e8cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - mortality</topic><topic>Adenocarcinoma - surgery</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Cancer therapies</topic><topic>CDX2 Transcription Factor</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Copy Number Variations</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Gene Amplification</topic><topic>Genetic testing</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>Pathology</topic><topic>Phenotype</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Retrospective Studies</topic><topic>SOXB1 Transcription Factors - genetics</topic><topic>SOXB1 Transcription Factors - metabolism</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - metabolism</topic><topic>Stomach Neoplasms - mortality</topic><topic>Stomach Neoplasms - surgery</topic><topic>Studies</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Camilo, Vânia</creatorcontrib><creatorcontrib>Barros, Rita</creatorcontrib><creatorcontrib>Celestino, Ricardo</creatorcontrib><creatorcontrib>Castro, Patrícia</creatorcontrib><creatorcontrib>Vieira, Joana</creatorcontrib><creatorcontrib>Teixeira, Manuel R</creatorcontrib><creatorcontrib>Carneiro, Fátima</creatorcontrib><creatorcontrib>Pinto-de-Sousa, João</creatorcontrib><creatorcontrib>David, Leonor</creatorcontrib><creatorcontrib>Almeida, Raquel</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMC cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Camilo, Vânia</au><au>Barros, Rita</au><au>Celestino, Ricardo</au><au>Castro, Patrícia</au><au>Vieira, Joana</au><au>Teixeira, Manuel R</au><au>Carneiro, Fátima</au><au>Pinto-de-Sousa, João</au><au>David, Leonor</au><au>Almeida, Raquel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome</atitle><jtitle>BMC cancer</jtitle><addtitle>BMC Cancer</addtitle><date>2014-10-09</date><risdate>2014</risdate><volume>14</volume><issue>1</issue><spage>753</spage><epage>753</epage><pages>753-753</pages><artnum>753</artnum><issn>1471-2407</issn><eissn>1471-2407</eissn><abstract>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.
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).
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.
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.</abstract><cop>England</cop><pub>BioMed Central</pub><pmid>25300947</pmid><doi>10.1186/1471-2407-14-753</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma - genetics Adenocarcinoma - metabolism Adenocarcinoma - mortality Adenocarcinoma - surgery Adult Aged Aged, 80 and over Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Cancer therapies CDX2 Transcription Factor Deoxyribonucleic acid DNA DNA Copy Number Variations Female Gastric cancer Gene Amplification Genetic testing Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Immunohistochemistry Kaplan-Meier Estimate Male Medical prognosis Middle Aged Pathology Phenotype Prognosis Proportional Hazards Models Retrospective Studies SOXB1 Transcription Factors - genetics SOXB1 Transcription Factors - metabolism Stomach Neoplasms - genetics Stomach Neoplasms - metabolism Stomach Neoplasms - mortality Stomach Neoplasms - surgery Studies Treatment Outcome Tumors Young Adult |
| title | Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome |
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