RESUMEN
Objective: To investigate the molecular markers of copy number aberrations (CNAs) of genes related to extrohepatic metastasis-free survival after the operation for hepatocellular carcinoma (HCC). Methods: The CNA status of 20 candidate genes in 66 HCC samples was detected by microarray comparative genomic hybridization. The associations between gene CNAs and extrohepatic metastasis-free survival were evaluated using the Cox regression model, Log-rank test, and Kaplan-Meier survival analysis. Results: Multivariate Cox analysis revealed that the independent risk factors for metastasis-free survival were MDM4 gain (hazard ratio [HR] = 2.74, 95% confidence interval [CI] = 1.18-6.37, P < 0.05), APC loss (HR = 8.43, 95% CI = 2.48-28.66, P < 0.01), and BCL2L1 gain (HR = 3.45, 95% CI = 1.13-10.52, P < 0.05) and the independent protective factor was FBXW7 loss (HR = 0.32, 95% CI = 0.12-0.89, P < 0.05). By stepwise Cox regression analysis, three CNAs related to metastasis-free survival were screened out: MDM4 gain (HR = 2.71, 95% CI = 1.11-6.64, P < 0.05), APC loss (HR = 7.19, 95% CI = 1.88-27.60, P < 0.005), and FBXW7 loss (HR = 0.16, 95% CI = 0.05-0.46, P < 0.01). There were significant differences in metastasis-free survival rate between the HCC patients with FBXW7 loss and without MDM4 gain or APC loss, those with MDM4 gain and/or APC loss and without FBXW7 loss, and those with other CNA combinations (log-rank test, P < 0.01). Conclusion: MDM4 gain, APC loss, and FBXW7 loss are the independent prognostic factors for extrohepatic metastasis-free survival after the operation for HCC and can be used to predict the risk of extrohepatic metastasis after the operation for HCC.
Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirugía , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Proteínas Nucleares/genética , Proteínas Proto-Oncogénicas/genética , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Proteínas de Ciclo Celular , Hibridación Genómica Comparativa , Variaciones en el Número de Copia de ADN/genética , Supervivencia sin Enfermedad , Proteína 7 que Contiene Repeticiones F-Box-WD/metabolismo , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Proteínas Nucleares/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas/metabolismo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Copy number alteration (CNA) of chromosome 16, a frequent genetic event in tumors including hepatocellular carcinoma (HCC), has been associated with HCC etiology of hepatitis B virus (HBV) and with clinical outcomes in multiple types of cancer. This study identified CNAs in chromosome 16 in relation to intrahepatic recurrence of HCC in a population with high HBV prevalence, and further screened for differentially expressed genes in recurrence-related CNAs. Array comparative genomic hybridization and expression arrays were used to detect CNAs and gene expression differences, respectively. The associations between CNAs and intrahepatic recurrence were analyzed on 66 patients, follow-up period of 3-73 months. One hundred and nine cases were further evaluated regarding the differentially expressed genes. Losses at 16q and 16p were detected in 62.1% and 51.5% of the 66 cases, respectively. The most recurrent CNAs (with frequency >20%) were losses at 16p13.3-13.2, 16p13.11, 16q11.2-22.1, 16q22.1, 16q22.2-24.2 and 16q24.2. Of the CNAs, 16q22.1 loss was significantly associated with unfavorable intrahepatic recurrence-free survival (P = 0.025). Multivariate Cox analysis identified 16q22.1 loss as an independent risk factor for intrahepatic recurrence (HR = 2.32, 95% CI = 1.26-4.27). A panel of 21 genes, including TRADD, PSMB10, THAP11, CTCF and ESRP2, were significantly downregulated in HCCs with 16q22.1 loss compared to those without the loss. These results suggest that loss at 16q22.1 was associated with increased risk for intrahepatic recurrence of HCC, at least in the HBV-prevalence population. Multiple downregulated genes correlated with the loss were screened.
Asunto(s)
Carcinoma Hepatocelular/genética , Genes Relacionados con las Neoplasias/genética , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/patología , Cromosomas Humanos Par 16/genética , Hibridación Genómica Comparativa , Variaciones en el Número de Copia de ADN , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Hepatitis B/complicaciones , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Clostridioides difficile is considered an urgent threat to human health by the US Centers for Disease Control and Prevention. In recent years, C. difficile has been reported increasingly as a cause of gastrointestinal disease in children, and the prevalence of hospital-acquired C. difficile infection and community-acquired CDI in children is increasing. AIM: To perform a systematic review and meta-analysis of risk factors for CDI in children. METHODS: MEDLINE/PubMed, EMBASE, Web of Science, Scopus, OVID, China National Knowledge Infrastructure, Wanfang (Chinese), SinoMed (Chinese) and Weipu (Chinese) were searched from inception to 12th January 2022. Observational studies (cohort, case-control and cross-sectional) on CDI in children were included in the analysis. Data were pooled using a fixed or random-effects model, and odds ratios (OR) were calculated. FINDINGS: In total, 25 observational studies were included in the analysis. Prior antibiotic exposure [OR 1.93, 95% confidence interval (CI) 1.25-2.97], prolonged hospitalization (OR 14.68, 95% CI 13.24-16.28), history of hospitalization (OR 3.67, 95% CI 1.91-7.06), gastric acid suppressants (OR 1.96, 95% CI 1.41-2.73), male gender (OR 1.18, 95% CI 1.05-1.32), neoplastic disease (OR 3.40, 95% CI, 2.85-4.07), immunodeficiency (OR 4.18, 95% CI 3.25-5.37), solid organ transplantation (OR 4.56, 95% CI 3.95-5.27) and enteral feeding (OR 2.21, 95% CI 1.05-4.62) were associated with increased risk of CDI. CONCLUSION: This systematic review and meta-analysis provides further evidence for the susceptibility factors of CDI to improve clinicians' awareness of CDI, and prevent C. difficile-associated diarrhoea in children.