Differentially Expressed Genes and Signaling Pathways Potentially Involved in Primary Resistance to Chemo-Immunotherapy in Advanced-Stage Gastric Cancer Patients
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Published:2022-12-20
Issue:1
Volume:24
Page:1
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Pinto Mauricio P.ORCID, Muñoz-Medel MatíasORCID, Retamal Ignacio N.ORCID, Bravo MariaLoreto, Latapiat VerónicaORCID, Córdova-Delgado MiguelORCID, Hill Charlotte N., Fernández M. Fernanda, Sánchez Carolina, Sáez Mauricio A., Martin Alberto J. M.ORCID, Morales-Pison Sebastián, Fernandez-Ramires Ricardo, García-Bloj Benjamín, Owen Gareth I.ORCID, Garrido Marcelo
Abstract
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.
Funder
FONDECYT Bristol Myers Squibb (BMS) Investigator Sponsored Research Centro Ciencia & Vida Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia de ANID Fondecyt Iniciacion
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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