Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report.
Adenocarcinoma
/ epidemiology
Adolescent
Adult
Aged
Aged, 80 and over
Codon
/ genetics
Colonic Neoplasms
/ epidemiology
Exons
Female
Follow-Up Studies
GTP Phosphohydrolases
/ genetics
Humans
Incidence
Male
Membrane Proteins
/ genetics
Middle Aged
Morocco
/ epidemiology
Mutation
Prognosis
Prospective Studies
Proto-Oncogene Proteins B-raf
/ genetics
Proto-Oncogene Proteins p21(ras)
/ genetics
Retrospective Studies
Sex Factors
Young Adult
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
12
09
2020
accepted:
27
02
2021
entrez:
30
3
2021
pubmed:
31
3
2021
medline:
14
10
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33784337
doi: 10.1371/journal.pone.0248522
pii: PONE-D-20-28747
pmc: PMC8009361
doi:
Substances chimiques
Codon
0
KRAS protein, human
0
Membrane Proteins
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
GTP Phosphohydrolases
EC 3.6.1.-
NRAS protein, human
EC 3.6.1.-
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0248522Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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