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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 ß 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-ß 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.
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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: DOCK3, FN1, PAPPA2, DNAH11, and FBN2. Furthermore, we evaluated a combined classification where CRC patients with at least one mutation in any of these genes were separated from the main cohort 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.
Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , Neoplasias Colorretais/genética , Mutação , Prognóstico , Biomarcadores Tumorais/genética , Taxa de Mutação , Proteínas do Tecido Nervoso/genética , Fatores de Troca do Nucleotídeo Guanina/genéticaRESUMO
Resumen Objetivo: Sintetizar las características epidemiológicas y clínicas de los niños de COVID-19 con EK, KLD y MIS-C. Métodos: Se realizó una búsqueda en 4 bases de datos y preprints hasta el 31 de Mayo del 2021. Se incluyeron reportes/series de caso que evaluaron las caracte rísticas clínicas del EK, KLD o MIS-C en pacientes pediátricos con COVID-19. Resultados: Se incluyeron 16 estudios (seis informes de casos y diez series de casos, 367 pacientes en total, 58 pacientes con EK, 87 con KLD y 290 pacientes con MIS-C); con edades entre los 6 meses y los 10 años, y el 62% eran mujeres. Se observó COVID-19 positivo en 75,2%. Respecto a EK, KLD y MIS-C, las características clínicas repor tadas fueron compatibles con los cuadros diagnósticos estandarizados en el contexto de COVID-19. La duración de la hospitalización fue de 5 a 14 días para EK y de 4,3 a 13 para MIS-C. Once pacientes con MIS-C (2,8%) necesitaron ECMO. Seis pacientes con MIS-C fueron reportados muertos. Ocho estudios reportaron pacientes en la UCI. Conclusiones: EK o KLD puede asociarse a COVID-19 en niños, y pueden complicarse con MIS-C. El tiempo de hospitalización es prolongado si se presenta EK o KLD asociado a COVID-19 en niños.
Abstract Objective: To synthesize the epidemiological and clinical characteristics of COVID-19 children with MIS-C, KLD and EK. Methods: Databases and preprints were searched until May 31, 2021. Reports/case series that evaluated the clinical features of EK, KLD, or MIS-C in pediatric patients with COVID-19 were included. Results: Sixteen studies were included (six case reports and ten case series, 367 patients total, 58 patients with EK, 87 with KLD, and 290 patients with MIS-C); with ages ranging from 6 months to 10 years, and 62% were female. Positive COVID-19 was observed in 75.2%. Regarding EK, KLD and MIS-C, the reported clinical characteristics were compatible with the standardized diagnostic pictures in the context of COVID-19. The duration of hospitalization was 5 to 14 days for EK and 4.3 to 13 for MIS-C. Eleven patients with MIS-C (2.8%) needed ECMO. Eleven patients with MIS-C (2.8%) needed ECMO. Six patients with MIS-C were reported dead. Eight studies reported patients in the ICU. Conclusions: Children with COVID-19 develop EK or KLD, and can be complicated by MIS-C. Prevention, diagnosis, and treatment measures are needed.
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Objetivo: El presente estudio se centró en determinar si la diferencia de hemoglobina del tercer y el primer trimestre de gestación mayor de 1 (Delta de hemoglobina disminuido) es un factor de riesgo para el bajo peso al nacer en recién nacidos a término en el Hospital Belén de Trujillo. Material y métodos: Estudio de cohorte histórica. Se realizó un estudio de cohorte retrospectiva donde se incluyeron 218 neonatos, de acuerdo con los criterios de selección, los cuales fueron divididos en dos grupos: pacientes con delta de hemoglobina materna disminuida y no disminuida: aplicando el riesgo relativo y el test estadístico de chi-cuadrado. Resultados: La frecuencia de neonatos con bajo peso al nacer en mujeres embarazadas con delta de hemoglobina disminuida fue de 32/109 = 29 %; la frecuencia de bajo peso al nacer en las mujeres embarazadas con delta de hemoglobina no disminuida fue de 18/109 = 17 %. La delta de hemoglobina materna disminuida es un factor de riesgo para el bajo peso al nacer con un riesgo relativo de 1.78 [IC: 95 % (1.45 3.56) p < 0.05]. Conclusiones: La delta de hemoglobina materna disminuida es un factor de riesgo para el bajo peso al nacer en recién nacidos a término en el Hospital Belén de Trujillo.
Objetive:The present study focused on determining if the hemoglobin difference of the third and first trimester of gestation greater than - 1 (decreased hemoglobin delta) is a risk factor for low birth weight in term newborns at Hospital Belen from Trujillo. We performed a retrospective cohort study in Material and Methods: which 218 newborns were included according to the selection criteria. The patients were divided into two group of patients with decreased and non-decreased maternal hemoglobin delta: applying the relative risk and the statistical chi test-square. The frequency of low birth weight in pregnant women with Results:decreased hemoglobin delta was 32/109 = 29%; the frequency of low birth weight in pregnant women with undiminished delta hemoglobin was 18/109 = 17%. Declined maternal hemoglobin delta is a risk factor for low birth weight with a relative risk of 1.78 [CI: 95% (1.45 - 3.56) p <0.05].The decreased maternal Conclusions:hemoglobin delta is a risk factor for low birth weight in newborns at Hospital Belen de Trujillo.
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BACKGROUND: COVID-19 can be asymptomatic in a substantial proportion of patients. The assessment and management of these patients constitute a key element to stop dissemination. AIM: To describe the assessment and treatment of asymptomatic infection in patients with a confirmed diagnosis of COVID-19. METHODS: We searched five databases and search engines for preprints/preproofs, up to August 22, 2020. We included cohort, cross-sectional, and case series studies, reporting the assessment and management of asymptomatic individuals. We extracted data on total discharges with negative PCR, length of hospitalization, treatment, and number of patients who remained asymptomatic. A random-effects model with inverse variance method was used to calculate the pooled prevalence. RESULTS: 41 studies (nine cross-sectional studies, five retrospective studies and 27 reports/case series; 647 asymptomatic individuals), were included, of which 47% were male (233/501). The age of patients was between 1month and 73 years. In patients who became symptomatic, length of hospitalization mean was 13.6 days (SD 6.4). Studies used lopinavir/ritonavir, hydroxychloroquine plus ritonavir/lopinavir, hydroxychloroquine with and without azithromycin, ribavirin plus interferon and interferon alfa. The proportion of individuals who remained asymptomatic was 91% (463/588 patients; 95%CI: 78.3%-98.7%); and asymptomatic individuals discharged with negative PCR was 86% (102/124 individuals; 95%CI: 58.4%-100%). CONCLUSIONS: There is no standard treatment for asymptomatic COVID-19 individuals. There are no studies of adequate design to make this decision. It has been shown that most asymptomatic individuals who were followed have recovered, but this cannot be attributed to standard treatment.