Influence of tumor stroma on the aggressiveness of poorly cohesive gastric carcinoma

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• dc.contributor.author Malpeli, Giorgio
• dc.contributor.author Filippini, Federica
• dc.contributor.author Tedone, Fabrizio
• dc.contributor.author Torroni, Lorena
• dc.contributor.author Alloggio, Mariella
• dc.contributor.author Castelli, Claudia
• dc.contributor.author Dal Cero, Mariagiulia
• dc.contributor.author Perris, Roberto
• dc.contributor.author Tomezzoli, Anna
• dc.contributor.author De Manzoni, Giovanni
• dc.contributor.author Bencivenga, Maria
• dc.date.accessioned 2024-10-25T06:09:54Z
• dc.date.available 2024-10-25T06:09:54Z
• dc.date.issued 2024
• dc.description.abstract Tumor-stroma crosstalk promotes the adaptation of cancer cells to the local microenvironment and sustains their growth. We assessed the quantitative and qualitative impact of intralesional stroma on clinic-pathological features and the prognosis of poorly cohesive gastric cancer (PCGC) variants. Tissue microarrays including 75 PCGC specimens were immunostained for cytokeratin 8/18 and α-smooth muscle actin to assess the relative proportion of neoplastic cells versus stromal components and the cases were subsequently divided into stroma-rich (SR) and stroma-poor (SP) tumors. Stromal status is significantly associated with the depth of tumor invasion. Patient survival rate was found to be higher in the SP compared to the SR tumor group and, hence, abundant stroma was identified as a significant risk factor in univariable analysis but had no independent prognostic impact. We also investigated the mRNA levels of KRT8 and the associated transcriptional signatures using the molecular data of 82 PCGC cases divided into KRT8-high and KRT8-low groups. KRT8-high tumors were enriched in proteins localized in the extracellular compartment and their expression levels correlated with longer survival in the KRT8-high group and shorter overall survival in the KRT8-low group. Comprehensively, we find that relative intralesional stromal content is a marker of aggressiveness in PCGC tumors and that extracellular proteins characterize functionally and clinically different PCGC subgroups.
• dc.format.mimetype application/pdf
• dc.identifier.citation Malpeli G, Filippini F, Tedone F, Torroni L, Alloggio M, Castelli C, et al. Influence of tumor stroma on the aggressiveness of poorly cohesive gastric carcinoma. J Pers Med. 2024 Feb 9;14(2):194. DOI: 10.3390/jpm14020194
• dc.identifier.doi http://dx.doi.org/10.3390/jpm14020194
• dc.identifier.issn 2075-4426
• dc.identifier.uri http://hdl.handle.net/10230/68352
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof J Pers Med. 2024 Feb 9;14(2):194
• dc.rights © 2024 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 Diffuse type
• dc.subject.keyword Gastric cancer
• dc.subject.keyword Intratumoral stroma
• dc.subject.keyword Poorly cohesive
• dc.title Influence of tumor stroma on the aggressiveness of poorly cohesive gastric carcinoma
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion