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Brief Bioinform ; 22(3)2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32743640

RESUMO

BACKGROUND: The most frequently mutated gene pairs in pancreatic adenocarcinoma (PAAD) are KRAS and TP53, and our goal is to illustrate the multiomics and molecular dynamics landscapes of KRAS/TP53 mutation and also to obtain prospective novel drugs for KRAS- and TP53-mutated PAAD patients. Moreover, we also made an attempt to discover the probable link amid KRAS and TP53 on the basis of the abovementioned multiomics data. METHOD: We utilized TCGA & Cancer Cell Line Encyclopedia data for the analysis of KRAS/TP53 mutation in a multiomics manner. In addition to that, we performed molecular dynamics analysis of KRAS and TP53 to produce mechanistic descriptions of particular mutations and carcinogenesis. RESULT: We discover that there is a significant difference in the genomics, transcriptomics, methylomics, and molecular dynamics pattern of KRAS and TP53 mutation from the matching wild type in PAAD, and the prognosis of pancreatic cancer is directly linked with a particular mutation of KRAS and protein stability. Screened drugs are potentially effective in PAAD patients. CONCLUSIONS: KRAS and TP53 prognosis of PAAD is directly associated with a specific mutation of KRAS. Irinotecan and vandetanib are prospective drugs for PAAD patients with KRASG12Dmutation and TP53 mutation.


Assuntos
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mutação , Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Intervalo Livre de Doença , Sinergismo Farmacológico , Feminino , Humanos , Irinotecano/administração & dosagem , Irinotecano/agonistas , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Piperidinas/administração & dosagem , Piperidinas/agonistas , Quinazolinas/administração & dosagem , Quinazolinas/agonistas , Taxa de Sobrevida
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