| Texto completo | |
| Autor(es): |
Sotomayor, Mariana Belen Velasquez
;
Segura, Anthony Vladimir Campos
;
Montalva, Ricardo Jose Asurza
;
Marin-Sanchez, Obert
;
Carrasco, Alexis German Murillo
;
Rojas, Cesar Alexander Ortiz
Número total de Autores: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | FRONTIERS IN GENETICS; v. 14, p. 15-pg., 2023-09-12. |
| Resumo | |
Gastric cancer (GC) ranks fifth in incidence and fourth in mortality worldwide. The high death rate in patients with GC requires new biomarkers for improving survival estimation. In this study, we performed a transcriptome-based analysis of five publicly available cohorts to identify genes consistently associated with prognosis in GC. Based on the ROC curve, patients were categorized into high and low-expression groups for each gene using the best cutoff point. Genes associated with survival (AUC > 0.5; univariate and multivariate Cox regressions, p < 0.05) were used to model gene expression-based scores by weighted sum using the pooled Cox beta regression coefficients. Cox regression (p < 0.05), AUC > 0.5, sensitivity > 0.5, and specificity > 0.5 were considered to identify the best scores. Gene set enrichment analysis (KEGG, REACTOME, and Gene Ontology databases), as well as microenvironment composition and stromal cell signatures prediction (CIBERSORT, EPIC, xCell, MCP-counter, and quanTIseq web tools) were performed. We found 11 genes related to GC survival in the five independent cohorts. Then, we modeled scores by calculating all possible combinations between these genes. Among the 2,047 scores, we identified a panel based on the expression of seven genes. It was named GES7 and is composed of CCDC91, DYNC1I1, FAM83D, LBH, SLITRK5, WTIP, and NAP1L3 genes. GES7 features were validated in two independent external cohorts. Next, GES7 was found to recategorize patients from AJCC TNM stages into a best-fitted prognostic group. The GES7 was associated with activation of the TGF-beta pathway and repression of anticancer immune cells. Finally, we compared the GES7 with 30 previous proposed scores, finding that GES7 is one of the most robust scores. As a result, the GES7 is a reliable gene-expression-based signature to improve the prognosis estimation in GC. (AU) | |
| Processo FAPESP: | 19/05583-0 - Enriquecimento de microvesículas extracelulares STn/Tn+ derivadas de tumor para avaliar marcadores baseados em miRNA em pacientes com Câncer de Mama |
| Beneficiário: | Alexis Germán Murillo Carrasco |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 17/08430-5 - Deteção dos transcritos do gene TP73 na Leucemia Promielocítica Aguda e seu impacto no prognóstico e resposta terapêutica |
| Beneficiário: | César Alexander Ortiz Rojas |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |