Impact of mini-driver genes in the prognosis and tumor features of colorectal cancer samples: a novel perspective to support current biomarkers

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art_SEGURA_Impact_of_minidriver_genes_in_the_prognosis_and_2023.PDF (7.79 MB)
Citações na Scopus
1
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
PEERJ INC
Autores
SEGURA, Anthony Vladimir Campos
SOTOMAYOR, Mariana Belen Velasquez
ROMAN, Ana Isabel Flor Gutierrez
ROJAS, Cesar Alexander Ortiz
Citação
PEERJ, v.11, article ID e15410, 19p, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths, and its development is associated with the gains and/or losses of genetic material, which leads to the emergence of main driver genes with higher mutational frequency. In addition, there are other genes with mutations that have weak tumor-promoting effects, known as mini-drivers, which could aggravate the development of oncogenesis when they occur together. The aim of our work was to use computer analysis to explore the survival impact, frequency, and incidence of mutations of possible mini-driver genes to be used for the prognosis of CRC. Methods: We retrieved data from three sources of CRC samples using the cBioPortal platform and analyzed the mutational frequency to exclude genes with driver features and those mutated in less than 5% of the original cohort. We also observed that the mutational profile of these mini-driver candidates is associated with variations in the expression levels. The candidate genes obtained were subjected to Kaplan-Meier curve analysis, making a comparison between mutated and wild-type samples for each gene using a p-value threshold of 0.01. Results: After gene filtering by mutational frequency, we obtained 159 genes of which 60 were associated with a high accumulation of total somatic mutations with Log2 (fold change) > 2 and p values < 10-5. In addition, these genes were enriched to oncogenic pathways such as epithelium-mesenchymal transition, hsa-miR-218-5p downregulation, and extracellular matrix organization. Our analysis identified five genes with possible implications as mini-drivers: DOCKS, FN1, PAPPA2, DNAH11, and FBN2. Furthermore, we evaluated a combined classification where CRC patients obtaining a p-value < 0.001 in the evaluation of CRC prognosis.Conclusion: Our study suggests that the identification and incorporation of mini-driver genes in addition to known driver genes could enhance the accuracy of prognostic biomarkers for CRC.
Palavras-chave
Mini-driver genes, Colorectal cancer, Bioinformatics, Molecular biology, Mutational profile, Gene expression
URI
https://observatorio.fm.usp.br/handle/OPI/54833
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Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - ODS/03