Differentially Expressed Genes and Signaling Pathways Potentially Involved in Primary Resistance to Chemo-Immunotherapy in Advanced-Stage Gastric Cancer Patients

Mauricio P. Pinto, Matías Muñoz-Medel, Ignacio N. Retamal, Maria Loreto Bravo, Verónica Latapiat, Miguel Córdova-Delgado, Charlotte N. Hill, M. Fernanda Fernández, Carolina Sánchez, Mauricio A. Sáez, Alberto J.M. Martin, Sebastián Morales-Pison, Ricardo Fernandez-Ramires, Benjamín García-Bloj, Gareth I. Owen, Marcelo Garrido*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

3 Citas (Scopus)

Resumen

Recently, the combination of chemotherapy plus nivolumab (chemo-immunotherapy) has become the standard of care for advanced-stage gastric cancer (GC) patients. However, despite its efficacy, up to 40% of patients do not respond to these treatments. Our study sought to identify variations in gene expression associated with primary resistance to chemo-immunotherapy. Diagnostic endoscopic biopsies were retrospectively obtained from advanced GC patients previously categorized as responders (R) or non-responders (NR). Thirty-four tumor biopsies (R: n = 16, NR: n = 18) were analyzed by 3′ massive analysis of cDNA ends (3′MACE). We found >30 differentially expressed genes between R and NRs. Subsequent pathway enrichment analyses demonstrated that angiogenesis and the Wnt-β-catenin signaling pathway were enriched in NRs. Concomitantly, we performed next generation sequencing (NGS) analyses in a subset of four NR patients that confirmed alterations in genes that belonged to the Wnt/β-catenin and the phosphoinositide 3-kinase (PI3K) pathways. We speculate that angiogenesis, the Wnt, and the PI3K pathways might offer actionable targets. We also discuss therapeutic alternatives for chemo-immunotherapy-resistant advanced-stage GC patients.

Idioma originalInglés
Número de artículo1
PublicaciónInternational Journal of Molecular Sciences
Volumen24
N.º1
DOI
EstadoPublicada - ene. 2023
Publicado de forma externa

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