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Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis

Mutations in the mismatch repair (MMR) system predict the response to immune checkpoint inhibitors (ICIs) like colon or gastric cancer. However, the MMR system’s involvement in non-small cell lung cancer (NSCLC) remains unknown. Addressing this issue will improve clinical guidelines in the case of m...

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Autores principales: Olivares-Hernández, Alejandro, del Barco Morillo, Edel, Parra Pérez, Carmen, Miramontes-González, José Pablo, Figuero-Pérez, Luis, Martín-Gómez, Teresa, Escala-Cornejo, Roberto, Bellido Hernández, Lorena, González Sarmiento, Rogelio, Cruz-Hernández, Juan Jesús, Ludeña de la Cruz, María Dolores
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962390/
https://www.ncbi.nlm.nih.gov/pubmed/35203569
http://dx.doi.org/10.3390/biomedicines10020360
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author Olivares-Hernández, Alejandro
del Barco Morillo, Edel
Parra Pérez, Carmen
Miramontes-González, José Pablo
Figuero-Pérez, Luis
Martín-Gómez, Teresa
Escala-Cornejo, Roberto
Bellido Hernández, Lorena
González Sarmiento, Rogelio
Cruz-Hernández, Juan Jesús
Ludeña de la Cruz, María Dolores
author_facet Olivares-Hernández, Alejandro
del Barco Morillo, Edel
Parra Pérez, Carmen
Miramontes-González, José Pablo
Figuero-Pérez, Luis
Martín-Gómez, Teresa
Escala-Cornejo, Roberto
Bellido Hernández, Lorena
González Sarmiento, Rogelio
Cruz-Hernández, Juan Jesús
Ludeña de la Cruz, María Dolores
author_sort Olivares-Hernández, Alejandro
collection PubMed
description Mutations in the mismatch repair (MMR) system predict the response to immune checkpoint inhibitors (ICIs) like colon or gastric cancer. However, the MMR system’s involvement in non-small cell lung cancer (NSCLC) remains unknown. Addressing this issue will improve clinical guidelines in the case of mutations in the main genes of the MMR system (MLH1, MSH2, MSH6, and PMS2). This work retrospectively assessed the role that these gene mutations play in the response to and survival of ICIs in NSCLC. Patients with NSCLC treated with nivolumab as the second-line treatment in the University Hospital of Salamanca were enrolled in this study. Survival and response analyses were performed according to groups of MMR system gene expression (MMR expression present or deficiency) and other subgroups, such as toxicity. There was a statistically significant relationship between the best response obtained and the expression of the MMR system (p = 0.045). The presence of toxicity grade ≥ 3 was associated with the deficiency expression of MMR (dMMR/MSI-H) group (p = 0.022; odds ratio = 10.167, 95% confidence interval (CI) 1.669–61.919). A trend towards greater survival and response to ICIs was observed in NSCLC and dMMR. Assessing the genes in the MMR system involved in NSCLC is key to obtaining personalized immunotherapy treatments.
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spelling pubmed-89623902022-03-30 Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis Olivares-Hernández, Alejandro del Barco Morillo, Edel Parra Pérez, Carmen Miramontes-González, José Pablo Figuero-Pérez, Luis Martín-Gómez, Teresa Escala-Cornejo, Roberto Bellido Hernández, Lorena González Sarmiento, Rogelio Cruz-Hernández, Juan Jesús Ludeña de la Cruz, María Dolores Biomedicines Article Mutations in the mismatch repair (MMR) system predict the response to immune checkpoint inhibitors (ICIs) like colon or gastric cancer. However, the MMR system’s involvement in non-small cell lung cancer (NSCLC) remains unknown. Addressing this issue will improve clinical guidelines in the case of mutations in the main genes of the MMR system (MLH1, MSH2, MSH6, and PMS2). This work retrospectively assessed the role that these gene mutations play in the response to and survival of ICIs in NSCLC. Patients with NSCLC treated with nivolumab as the second-line treatment in the University Hospital of Salamanca were enrolled in this study. Survival and response analyses were performed according to groups of MMR system gene expression (MMR expression present or deficiency) and other subgroups, such as toxicity. There was a statistically significant relationship between the best response obtained and the expression of the MMR system (p = 0.045). The presence of toxicity grade ≥ 3 was associated with the deficiency expression of MMR (dMMR/MSI-H) group (p = 0.022; odds ratio = 10.167, 95% confidence interval (CI) 1.669–61.919). A trend towards greater survival and response to ICIs was observed in NSCLC and dMMR. Assessing the genes in the MMR system involved in NSCLC is key to obtaining personalized immunotherapy treatments. MDPI 2022-02-02 /pmc/articles/PMC8962390/ /pubmed/35203569 http://dx.doi.org/10.3390/biomedicines10020360 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Olivares-Hernández, Alejandro
del Barco Morillo, Edel
Parra Pérez, Carmen
Miramontes-González, José Pablo
Figuero-Pérez, Luis
Martín-Gómez, Teresa
Escala-Cornejo, Roberto
Bellido Hernández, Lorena
González Sarmiento, Rogelio
Cruz-Hernández, Juan Jesús
Ludeña de la Cruz, María Dolores
Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis
title Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis
title_full Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis
title_fullStr Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis
title_full_unstemmed Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis
title_short Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis
title_sort influence of dna mismatch repair (mmr) system in survival and response to immune checkpoint inhibitors (icis) in non-small cell lung cancer (nsclc): retrospective analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962390/
https://www.ncbi.nlm.nih.gov/pubmed/35203569
http://dx.doi.org/10.3390/biomedicines10020360
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