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

doi:10.3390/ijms24010001

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 revista › Artículo › revisión 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 original	Inglés
Número de artículo	1
Publicación	International Journal of Molecular Sciences
Volumen	24
N.º	1
DOI	https://doi.org/10.3390/ijms24010001
Estado	Publicada - 2023

Nota bibliográfica

Funding Information:
This research was funded by FONDECYT grants #1180173 and #1221499, by a Bristol Myers Squibb (BMS) Investigator Sponsored Research grant #ISR CA209-8F3 (to M.G.), and by FONDECYT grant ##1220586 and ANID/MIII ICN09-016/ICN 2021-045; ANID/FONDAP-ACCDIS 1513001 (G.I.O.). Also, Centro Ciencia & Vida, FB210008; Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia de ANID (A.J.M.M.); and Fondecyt Iniciacion grant #11171015 (M.A.S.).

Publisher Copyright:
© 2022 by the authors.

Áreas temáticas de ASJC Scopus

Catálisis
Biología molecular
Espectroscopia
Informática aplicada
Química física y teórica
Química orgánica
Química inorgánica

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Acceder al documento

10.3390/ijms24010001

Otros archivos y enlaces

Enlace a la publicación en Scopus

Citar esto

Pinto, M. P., Muñoz-Medel, M., Retamal, I. N., Bravo, M. L., Latapiat, V., Córdova-Delgado, M., Hill, C. N., Fernández, M. F., Sánchez, C., Sáez, M. A., Martin, A. J. M., Morales-Pison, S., Fernandez-Ramires, R., García-Bloj, B., Owen, G. I., & Garrido, M. (2023). Differentially Expressed Genes and Signaling Pathways Potentially Involved in Primary Resistance to Chemo-Immunotherapy in Advanced-Stage Gastric Cancer Patients. International Journal of Molecular Sciences, 24(1), Artículo 1. https://doi.org/10.3390/ijms24010001

@article{33a9e1f3508645a28e7dfc9374a4d693,

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

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.",

keywords = "angiogenesis, cancer therapy, gastric cancer, immunotherapy resistance, molecular oncology, PI3K pathway, Wnt pathway, β-catenin",

author = "Pinto, {Mauricio P.} and Mat{\'i}as Mu{\~n}oz-Medel and Retamal, {Ignacio N.} and Bravo, {Maria Loreto} and Ver{\'o}nica Latapiat and Miguel C{\'o}rdova-Delgado and Hill, {Charlotte N.} and Fern{\'a}ndez, {M. Fernanda} and Carolina S{\'a}nchez and S{\'a}ez, {Mauricio A.} and Martin, {Alberto J.M.} and Sebasti{\'a}n Morales-Pison and Ricardo Fernandez-Ramires and Benjam{\'i}n Garc{\'i}a-Bloj and Owen, {Gareth I.} and Marcelo Garrido",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2023",

month = jan,

doi = "10.3390/ijms24010001",

language = "English",

volume = "24",

journal = "International Journal of Molecular Sciences",

issn = "1661-6596",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "1",

}

Pinto, MP, Muñoz-Medel, M, Retamal, IN, Bravo, ML, Latapiat, V, Córdova-Delgado, M, Hill, CN, Fernández, MF, Sánchez, C, Sáez, MA, Martin, AJM, Morales-Pison, S, Fernandez-Ramires, R, García-Bloj, B, Owen, GI & Garrido, M 2023, 'Differentially Expressed Genes and Signaling Pathways Potentially Involved in Primary Resistance to Chemo-Immunotherapy in Advanced-Stage Gastric Cancer Patients', International Journal of Molecular Sciences, vol. 24, n.º 1, 1. https://doi.org/10.3390/ijms24010001

Differentially Expressed Genes and Signaling Pathways Potentially Involved in Primary Resistance to Chemo-Immunotherapy in Advanced-Stage Gastric Cancer Patients. / Pinto, Mauricio P.; Muñoz-Medel, Matías; Retamal, Ignacio N. et al.
En: International Journal of Molecular Sciences, Vol. 24, N.º 1, 1, 01.2023.

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

TY - JOUR

T1 - Differentially Expressed Genes and Signaling Pathways Potentially Involved in Primary Resistance to Chemo-Immunotherapy in Advanced-Stage Gastric Cancer Patients

AU - Pinto, Mauricio P.

AU - Muñoz-Medel, Matías

AU - Retamal, Ignacio N.

AU - Bravo, Maria Loreto

AU - Latapiat, Verónica

AU - Córdova-Delgado, Miguel

AU - Hill, Charlotte N.

AU - Fernández, M. Fernanda

AU - Sánchez, Carolina

AU - Sáez, Mauricio A.

AU - Martin, Alberto J.M.

AU - Morales-Pison, Sebastián

AU - Fernandez-Ramires, Ricardo

AU - García-Bloj, Benjamín

AU - Owen, Gareth I.

AU - Garrido, Marcelo

PY - 2023/1

Y1 - 2023/1

N2 - 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.

AB - 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.

KW - angiogenesis

KW - cancer therapy

KW - gastric cancer

KW - immunotherapy resistance

KW - molecular oncology

KW - PI3K pathway

KW - Wnt pathway

KW - β-catenin

UR - http://www.scopus.com/inward/record.url?scp=85145978931&partnerID=8YFLogxK

U2 - 10.3390/ijms24010001

DO - 10.3390/ijms24010001

M3 - Article

C2 - 36613445

AN - SCOPUS:85145978931

SN - 1661-6596

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 1

M1 - 1

ER -

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

Resumen

Nota bibliográfica

Áreas temáticas de ASJC Scopus

ODS de las Naciones Unidas

Acceder al documento

Otros archivos y enlaces

Huella

Citar esto