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Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report

This study aimed to estimate the incidence of KRAS, NRAS, and BRAF mutations in the Moroccan population, and investigate the associations of KRAS and NRAS gene mutations with clinicopathological characteristics and their prognosis value. To achieve these objectives, we reviewed medical and pathology...

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Autores principales: El agy, Fatima, el Bardai, Sanae, El Otmani, Ihsane, Benbrahim, Zineb, Karim, Ibn Majdoub Hassani, Mazaz, Khalid, Benjelloun, El Bachir, Ousadden, Abdelmalek, El Abkari, Mohammed, Ibrahimi, Sidi Adil, Chbani, Laila
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009361/
https://www.ncbi.nlm.nih.gov/pubmed/33784337
http://dx.doi.org/10.1371/journal.pone.0248522
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author El agy, Fatima
el Bardai, Sanae
El Otmani, Ihsane
Benbrahim, Zineb
Karim, Ibn Majdoub Hassani
Mazaz, Khalid
Benjelloun, El Bachir
Ousadden, Abdelmalek
El Abkari, Mohammed
Ibrahimi, Sidi Adil
Chbani, Laila
author_facet El agy, Fatima
el Bardai, Sanae
El Otmani, Ihsane
Benbrahim, Zineb
Karim, Ibn Majdoub Hassani
Mazaz, Khalid
Benjelloun, El Bachir
Ousadden, Abdelmalek
El Abkari, Mohammed
Ibrahimi, Sidi Adil
Chbani, Laila
author_sort El agy, Fatima
collection PubMed
description This study aimed to estimate the incidence of KRAS, NRAS, and BRAF mutations in the Moroccan population, and investigate the associations of KRAS and NRAS gene mutations with clinicopathological characteristics and their prognosis value. To achieve these objectives, we reviewed medical and pathology reports for 210 patients. RAS testing was investigated by Sanger sequencing and Pyrosequencing technology. BRAF (exon 15) status was analyzed by the Sanger method. The expression of MMR proteins was evaluated by Immunohistochemistry. KRAS and NRAS mutations were found in 36.7% and 2.9% of 210 patients, respectively. KRAS exon 2 mutations were identified in 76.5% of the cases. RAS-mutated colon cancers were significantly associated with female gender, presence of vascular invasion, classical adenocarcinoma, moderately differentiated tumors, advanced TNM stage III-IV, left colon site, higher incidence of distant metastases at the time of diagnostic, microsatellite stable phenotype, lower number of total lymph nodes, and higher means of positive lymph nodes and lymph node ratio. KRAS exon 2-mutated colon cancers, compared with KRAS wild-type colon cancers were associated with the same clinicopathological features of RAS-mutated colon cancers. NRAS-mutated patients were associated with lower total lymph node rate and the presence of positive lymph node. Rare RAS-mutated tumors, compared with wild-type tumors were more frequently moderately differentiated and associated with lower lymph node rate. We found that KRAS codon 13-mutated, tumors compared to codon 12-mutated tumors were significantly correlated with a higher death cases number, a lower rate of positive lymph, lower follow-up time, and poor overall survival. Our findings show that KRAS and NRAS mutations have distinct clinicopathological features. KRAS codon 13-mutated status was the worst predictor of prognosis at all stages in our population.
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spelling pubmed-80093612021-04-07 Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report El agy, Fatima el Bardai, Sanae El Otmani, Ihsane Benbrahim, Zineb Karim, Ibn Majdoub Hassani Mazaz, Khalid Benjelloun, El Bachir Ousadden, Abdelmalek El Abkari, Mohammed Ibrahimi, Sidi Adil Chbani, Laila PLoS One Research Article This study aimed to estimate the incidence of KRAS, NRAS, and BRAF mutations in the Moroccan population, and investigate the associations of KRAS and NRAS gene mutations with clinicopathological characteristics and their prognosis value. To achieve these objectives, we reviewed medical and pathology reports for 210 patients. RAS testing was investigated by Sanger sequencing and Pyrosequencing technology. BRAF (exon 15) status was analyzed by the Sanger method. The expression of MMR proteins was evaluated by Immunohistochemistry. KRAS and NRAS mutations were found in 36.7% and 2.9% of 210 patients, respectively. KRAS exon 2 mutations were identified in 76.5% of the cases. RAS-mutated colon cancers were significantly associated with female gender, presence of vascular invasion, classical adenocarcinoma, moderately differentiated tumors, advanced TNM stage III-IV, left colon site, higher incidence of distant metastases at the time of diagnostic, microsatellite stable phenotype, lower number of total lymph nodes, and higher means of positive lymph nodes and lymph node ratio. KRAS exon 2-mutated colon cancers, compared with KRAS wild-type colon cancers were associated with the same clinicopathological features of RAS-mutated colon cancers. NRAS-mutated patients were associated with lower total lymph node rate and the presence of positive lymph node. Rare RAS-mutated tumors, compared with wild-type tumors were more frequently moderately differentiated and associated with lower lymph node rate. We found that KRAS codon 13-mutated, tumors compared to codon 12-mutated tumors were significantly correlated with a higher death cases number, a lower rate of positive lymph, lower follow-up time, and poor overall survival. Our findings show that KRAS and NRAS mutations have distinct clinicopathological features. KRAS codon 13-mutated status was the worst predictor of prognosis at all stages in our population. Public Library of Science 2021-03-30 /pmc/articles/PMC8009361/ /pubmed/33784337 http://dx.doi.org/10.1371/journal.pone.0248522 Text en © 2021 El agy et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
El agy, Fatima
el Bardai, Sanae
El Otmani, Ihsane
Benbrahim, Zineb
Karim, Ibn Majdoub Hassani
Mazaz, Khalid
Benjelloun, El Bachir
Ousadden, Abdelmalek
El Abkari, Mohammed
Ibrahimi, Sidi Adil
Chbani, Laila
Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report
title Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report
title_full Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report
title_fullStr Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report
title_full_unstemmed Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report
title_short Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report
title_sort mutation status and prognostic value of kras and nras mutations in moroccan colon cancer patients: a first report
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009361/
https://www.ncbi.nlm.nih.gov/pubmed/33784337
http://dx.doi.org/10.1371/journal.pone.0248522
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