Influence of Tumor Stroma on the Aggressiveness of Poorly Cohesive Gastric Carcinoma
Malpeli, Giorgio (Università telematica San Raffaele (Roma, Itàlia))
Filippini, Federica (Università di Verona (Itàlia))
Tedone, Fabrizio (Università di Verona (Itàlia))
Torroni, Lorena (Università di Verona (Itàlia))
Alloggio, Mariella (Università di Verona (Itàlia))
Castelli, Claudia (Verona University Hospital)
Dal Cero, Mariagiulia (Institut Hospital del Mar d'Investigacions Mèdiques)
Perris, Roberto (Università di Parma (Itàlia))
Tomezzoli, Anna (Verona University Hospital)
De Manzoni, Giovanni (Università di Verona (Itàlia))
Bencivenga, Maria (Università di Verona (Itàlia))
Universitat Autònoma de Barcelona

Date:	2024
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Diffuse type ; Gastric cancer ; Intratumoral stroma ; Poorly cohesive
Published in:	Journal of personalized medicine, Vol. 14 (february 2024) , ISSN 2075-4426

DOI: 10.3390/jpm14020194
PMID: 38392627

13 p, 2.9 MB

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