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dc.creatorAlmeida, GM
dc.creatorPereira, C
dc.creatorPark, JH
dc.creatorLemos, C
dc.creatorCampelos, S
dc.creatorGullo, I
dc.creatorMartins, D
dc.creatorGonçalves, G
dc.creatorLeitão, D
dc.creatorNeto, JL
dc.creatorAndré, A
dc.creatorBorges, C
dc.creatorAlmeida, D
dc.creatorLee, HJ
dc.creatorKong, SH
dc.creatorKim, WH
dc.creatorCarneiro, F
dc.creatorAlmeida, R
dc.creatorYang, HK
dc.creatorOliveira, C
dc.description.abstractIn 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 1.002–2.131). Patients with high CD44v6 tumor expression benefited from conventional chemotherapy in addition to surgery (p < 0.05), particularly those with heterogeneous CD44v6-positive and-negative populations (CD44v6_3+) (p < 0.007 and p < 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.
dc.description.sponsorshipThis work was funded by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020–Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT–Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). This work was also financed by the projects NORTE-01-0145-FEDER-000003 and NORTE-01-0145-FEDER-000029, supported by the Norte Portugal Regional Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); project POCI-01-0145-FEDER-016390 and SAICTPAC/0022/2015, funded by ERDF, POCI, and FCT; project PTDC/CTM-NAN/120958/2010, from FCT; and by project PTDC/BTM-TEC/30164/2017 funded by ERDF funds through the COMPETE 2020–POCI, Portugal 2020, and by FCT. Salary support to G.M.A. by PTDC/BTM-TEC/30164/2017 project; C.P. was supported by the grant SFRH/BD/113031/2015 from FCT.
dc.relationinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/SAICTPAC%2F0022%2F2015/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FBTM-TEC%2F30164%2F2017/PT
dc.relation.ispartofBiomedicines, vol.9(9):1249
dc.subjectConventional chemotherapy
dc.subjectDrug therapy
dc.subjectGastric surgery
dc.subjectGenetic heterogeneity
dc.subjectStomach neoplasms
dc.titleCd44v6 high membranous expression is a predictive marker of therapy response in gastric cancer patients
dc.typeArtigo em Revista Científica Internacional
dc.contributor.uportoInstituto de Investigação e Inovação em Saúde
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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