{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T12:21:56Z","timestamp":1764937316347,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T00:00:00Z","timestamp":1631923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)","award":["NORTE-01-0145-FEDER-000003","NORTE-01-0145-FEDER-000029"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000003","NORTE-01-0145-FEDER-000029"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["(PTDC\/CTM-NAN\/120958\/2010","SFRH\/BD\/113031\/2015"],"award-info":[{"award-number":["(PTDC\/CTM-NAN\/120958\/2010","SFRH\/BD\/113031\/2015"]}]},{"name":"PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)","award":["POCI-01-0145-FEDER-016390 and SAICTPAC\/0022\/2015"],"award-info":[{"award-number":["POCI-01-0145-FEDER-016390 and SAICTPAC\/0022\/2015"]}]},{"name":"ERDF funds through the COMPETE 2020 - POCI, Portugal 2020 and by FCT","award":["PTDC\/BTM-TEC\/30164\/2017"],"award-info":[{"award-number":["PTDC\/BTM-TEC\/30164\/2017"]}]},{"name":"FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020\u2013Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT\u2013Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia\/Minist\u00e9rio","award":["POCI-01-0145-FEDER-007274"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007274"]}]},{"name":"ERDF, POCI and FCT","award":["POCI-01-0145-FEDER-016390 and SAICTPAC\/0022\/2015"],"award-info":[{"award-number":["POCI-01-0145-FEDER-016390 and SAICTPAC\/0022\/2015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>In gastric cancer (GC), biomarkers that define prognosis and predict treatment response remain scarce. We hypothesized that the extent of CD44v6 membranous tumor expression could predict prognosis and therapy response in GC patients. Two GC surgical cohorts, from Portugal and South Korea (n = 964), were characterized for the extension of CD44v6 membranous immuno-expression, clinicopathological features, patient survival, and therapy response. The value of CD44v6 expression in predicting response to treatment and its impact on prognosis was determined. High CD44v6 expression was associated with invasive features (perineural invasion and depth of invasion) in both cohorts and with worse survival in the Portuguese GC cohort (HR 1.461; 95% confidence interval 1.002\u20132.131). Patients with high CD44v6 tumor expression benefited from conventional chemotherapy in addition to surgery (p &lt; 0.05), particularly those with heterogeneous CD44v6-positive and -negative populations (CD44v6_3+) (p &lt; 0.007 and p &lt; 0.009). Our study is the first to identify CD44v6 high membranous expression as a potential predictive marker of response to conventional treatment, but it does not clarify CD44v6 prognostic value in GC. Importantly, our data support selection of GC patients with high CD44v6-expressing tumors for conventional chemotherapy in addition to surgery. These findings will allow better stratification of GC patients for treatment, potentially improving their overall survival.<\/jats:p>","DOI":"10.3390\/biomedicines9091249","type":"journal-article","created":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T07:52:14Z","timestamp":1632124334000},"page":"1249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["CD44v6 High Membranous Expression Is a Predictive Marker of Therapy Response in Gastric Cancer Patients"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8712-7394","authenticated-orcid":false,"given":"Gabriela M","family":"Almeida","sequence":"first","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5892-0764","authenticated-orcid":false,"given":"Carla","family":"Pereira","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"Doctoral Programme in Biomedicine, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6811-8895","authenticated-orcid":false,"given":"Ji-Hyeon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Surgery, Seoul National University Hospital, Seoul 03080, Korea"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9803-9584","authenticated-orcid":false,"given":"Carolina","family":"Lemos","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"UnIGENe, IBMC\u2014Institute for Molecular and Cell Biology, 4200-135 Porto, Portugal"},{"name":"ICBAS\u2014Instituto Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6847-5630","authenticated-orcid":false,"given":"Sofia","family":"Campelos","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Department of Pathology, Ipatimup Diagnostics, Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3377-0530","authenticated-orcid":false,"given":"Irene","family":"Gullo","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Pathology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1457-8992","authenticated-orcid":false,"given":"Diana","family":"Martins","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Biomedical Laboratory Sciences, ESTeSC\u2014Coimbra Health School, Polytechnic Institute of Coimbra, 3046-854 Coimbra, Portugal"}]},{"given":"Gilza","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Dina","family":"Leit\u00e3o","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Pathology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0863-158X","authenticated-orcid":false,"given":"Jo\u00e3o Lu\u00eds","family":"Neto","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0638-8304","authenticated-orcid":false,"given":"Ana","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Clara","family":"Borges","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8373-3917","authenticated-orcid":false,"given":"Daniela","family":"Almeida","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9530-647X","authenticated-orcid":false,"given":"Hyuk-Joon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Cancer Research Institute, Seoul National University, Seoul 03080, Korea"},{"name":"Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea"}]},{"given":"Seong-Ho","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0557-1016","authenticated-orcid":false,"given":"Woo Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1964-1006","authenticated-orcid":false,"given":"F\u00e1tima","family":"Carneiro","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Pathology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-1633","authenticated-orcid":false,"given":"Raquel","family":"Almeida","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"given":"Han-Kwang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Cancer Research Institute, Seoul National University, Seoul 03080, Korea"},{"name":"Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8340-2264","authenticated-orcid":false,"given":"Carla","family":"Oliveira","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Ipatimup\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, 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