YAP activation is associated with a worse prognosis of poorly cohesive gastric cancer
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- dc.contributor.author Bencivenga, Maria
- dc.contributor.author Torroni, Lorena
- dc.contributor.author Dal Cero, Mariagiulia
- dc.contributor.author Quinzii, Alberto
- dc.contributor.author Zecchetto, Camilla
- dc.contributor.author Merz, Valeria
- dc.contributor.author Casalino, Simona
- dc.contributor.author Taus, Francesco
- dc.contributor.author Pietrobono, Silvia
- dc.contributor.author Mangiameli, Domenico
- dc.contributor.author Filippini, Federica
- dc.contributor.author Alloggio, Mariella
- dc.contributor.author Castelli, Claudia
- dc.contributor.author Iglesias Coma, Mar
- dc.contributor.author Pera Roman, Manuel Ramón
- dc.contributor.author Melisi, Davide
- dc.date.accessioned 2024-03-22T08:23:05Z
- dc.date.available 2024-03-22T08:23:05Z
- dc.date.issued 2023
- dc.description.abstract Poorly cohesive (PC) gastric cancer (GC) is extremely aggressive in progression, and there is an urgent need to identify the molecular pathways involved. We hypothesized the essential role of the RhoA-YAP axis in these mechanisms. The present observational multicenter retrospective study included 133 patients with PC GC treated at two dedicated European surgical centers between 2004 and 2014. YAP nuclear localization was measured by immunohistochemical (IHC) analysis of tissue biopsies. The complete absence of nuclear reactivity was coded as negative expression; we considered "any positive" as low nuclear expression (>0% but <10% of cells) and high nuclear expression (≥10% of cells). Women represented about half of the present series (52%), and the median age was 64 years (p25-p75 range: 53-75). Neoadjuvant and adjuvant treatments were administered to 10% and 54% of the cases, respectively. Extended systemic lymphadenectomy (D2) was the most common (54%). In nearly all cases, the number of retrieved nodes was ≥15, i.e., adequate for tumor staging (94%). An R0 resection was achieved in 80% of the cases. Most patients were pathological T stage 3 and 4 (pT3/pT4 = 79.0%) and pathological N stage 2, 3a, and 3b (pN2/pN3a/pN3b = 47.0%) at the pathological examination. Twenty patients (15%) presented distant metastases. Five-year overall survival (OS) was significantly higher (p = 0.029) in patients with negative YAP (46%, 95% CI 31.1-60.0%) than in the other patients (27%, 17.5-38.1%). Moreover, when controlling for sex, age, pT, pN, and percentage of signet ring cells in the multivariable analysis, YAP expression was a significant predictor of OS (HR 2.03, 95% CI: 1.18-3.51, p = 0.011). Our results provide new insights into the role of the YAP signaling cascade, as its activation was associated with a worse prognosis in PC GC.
- dc.format.mimetype application/pdf
- dc.identifier.citation Bencivenga M, Torroni L, Dal Cero M, Quinzii A, Zecchetto C, Merz V, et al. YAP activation is associated with a worse prognosis of poorly cohesive gastric cancer. J Pers Med. 2023 Aug 24;13(9):1294. DOI: 10.3390/jpm13091294
- dc.identifier.doi http://dx.doi.org/10.3390/jpm13091294
- dc.identifier.issn 2075-4426
- dc.identifier.uri http://hdl.handle.net/10230/59523
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof J Pers Med. 2023 Aug 24;13(9):1294
- dc.rights © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword YAP expression
- dc.subject.keyword Gastric cancer
- dc.subject.keyword Poorly cohesive
- dc.subject.keyword Tumor progression
- dc.title YAP activation is associated with a worse prognosis of poorly cohesive gastric cancer
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion