RESUMEN
Enoyl coenzyme A hydratase short chain 1 (ECHS1) is an important part of the mitochondrial fatty acid ß-oxidation pathway. Altered ECHS1 expression has been implicated in cancer cell proliferation. This study assessed ECHS1 expression in human gastric cancer cell lines and investigated the effects of ECHS1 knockdown on gastric cancer cell proliferation and migration. The human gastric cancer cell lines SGC-7901, BGC-823 and MKN-28, and the immortalized human gastric epithelial mucosa GES-1 cell line were analyzed for ECHS1 protein levels using western blot. The effectiveness of ECHS1-RNA interference was also determined using western blot. Proliferation and migration of the siECHS1 cells were respectively measured with the CCK-8 and transwell assays. Phosphorylation of PKB and GSK3ß was assessed using western blot. ECHS1 protein levels were significantly higher in poorly differentiated cells than in well-differentiated cells and immortalized gastric epithelial mucosa cells. Stable expression of ECHS1 shRNA was associated with an over 41% reduction in the ECHS1 protein levels of siECHS1 cells. Constitutive knockdown of the ECHS1 gene in siECHS1 cells was associated with significantly inhibited cell proliferation and migration. We also observed decreased levels of PKB and GSK3ß phosphorylation in siECHS1 cells. ECHS1 expression is increased in human gastric cancer cells. Increased ECHS1 expression activates PKB and GSK3ß by inducing the phosphorylation of the two kinases. ECHS1 may play important roles in gastric cancer cell proliferation and migration through PKB- and GSK3ß-related signaling pathways.
Asunto(s)
Movimiento Celular , Proliferación Celular , Enoil-CoA Hidratasa/genética , Diferenciación Celular , Línea Celular Tumoral , Enoil-CoA Hidratasa/metabolismo , Expresión Génica , Técnicas de Silenciamiento del Gen , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Células HEK293 , Humanos , Fosforilación , Procesamiento Proteico-Postraduccional , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Neoplasias GástricasRESUMEN
Overexpression of ECHS1 occurs in different cancers, including hepatocellular carcinoma (HCC). ECHS1 is also reported to have an oncogenic activity in various human cancers. This study investigated the effect of ECHS1 knockdown on the regulation of HCC growth. ECHS1 shRNA suppressed the expression of ECHS1 protein in HepG2 cells compared to the negative control vector-transfected HCC cells. ECHS1 knockdown also reduced HCC cell viability and enhanced cisplatin-induced apoptosis in HCC cells. Akt activation and the expression of various cell cycle-related genes were inhibited following ECHS1 knockdown. ECHS1 shRNA suppressed hepatocellular carcinoma growth in tumor xenograft mice. These data demonstrate that ECHS1 may play a role in HCC progression, suggesting that inhibition of ECHS1 expression using ECHS1 shRNA should be further evaluated as a novel target for the control of HCC.
Asunto(s)
Proliferación Celular , Enoil-CoA Hidratasa/genética , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genética , Animales , Apoptosis , Carcinoma Hepatocelular/genética , Movimiento Celular , Supervivencia Celular , Células Cultivadas , Cisplatino , Enoil-CoA Hidratasa/metabolismo , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células Hep G2 , Humanos , Etiquetado Corte-Fin in Situ , Neoplasias Hepáticas/genética , Masculino , Ratones , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismoRESUMEN
The present study aimed to construct and evaluate a novel experiment-based hypoxia signature to help evaluations of GBM patient status. First, the 426 proteins, which were previously found to be differentially expressed between normal and hypoxia groups in glioblastoma cells with statistical significance, were converted into the corresponding genes, among which 212 genes were found annotated in TCGA. Second, after evaluated by single-variable Cox analysis, 19 different expressed genes (DEGs) with prognostic value were identified. Based on λ value by LASSO, a gene-based survival risk score model, named RiskScore, was built by 7 genes with LASSO coefficient, which were FKBP2, GLO1, IGFBP5, NSUN5, RBMX, TAGLN2 and UBE2V2. Kaplan-Meier (K-M) survival curve analysis and the area under the curve (AUC) were plotted to further estimate the efficacy of this risk score model. Furthermore, the survival curve analysis was also plotted based on the subtypes of age, IDH, radiotherapy and chemotherapy. Meanwhile, immune infiltration, GSVA, GSEA and chemo drug sensitivity of this risk score model were evaluated. Third, the 7 genes expression were evaluated by AUC, overall survival (OS) and IDH subtype in datasets, importantly, also experimentally verified in GBM cell lines exposed to hypoxic or normal oxygen condition, which showed significant higher expression in hypoxia than in normal group. Last, combing the hypoxia RiskScore with clinical and molecular features, a prognostic composite nomogram was generated, showing the good sensitivity and specificity by AUC and OS. Meanwhile, univariate analysis and multivariate analysis were used for performed to identify variables in nomogram that were significant in independently predicting duration of survival. It is a first time that we successfully established and validated an independent prognostic risk model based on hypoxia microenvironment from glioblastoma cells and public database. The 7 key genes may provide potential directions for future biochemical and pharmaco-therapeutic research.
Asunto(s)
Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Proteoma/metabolismo , Proteómica/métodos , Microambiente Tumoral/genética , Anciano , Línea Celular Tumoral , Bases de Datos Factuales/estadística & datos numéricos , Femenino , Perfilación de la Expresión Génica/estadística & datos numéricos , Glioblastoma/diagnóstico , Glioblastoma/metabolismo , Humanos , Hipoxia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nomogramas , Farmacogenética/métodos , Farmacogenética/estadística & datos numéricos , Pronóstico , Proteoma/genética , Proteómica/estadística & datos numéricosRESUMEN
Because the study population with gliosarcoma (GSM) is limited, the understanding of this disease is insufficient. In this study, the authors aimed to determine the clinical characteristics and independent prognostic factors influencing the prognosis of GSM patients and to develop a nomogram to predict the prognosis of GSM patients after craniotomy. A total of 498 patients diagnosed with primary GSM between 2004 and 2015 were extracted from the 18 Registries Research Data of the Surveillance, Epidemiology, and End Results (SEER) database. The median disease-specific survival (DSS) was 12.0 months, and the postoperative 0.5-, 1-, and 3-year DSS rates were 71.4%, 46.4% and 9.8%, respectively. We applied both the Cox proportional hazards model and the decision tree model to determine the prognostic factors of primary GSM. The Cox proportional hazards model demonstrated that age at presentation, tumour size, metastasis state and adjuvant chemotherapy (CT) were independent prognostic factors for DSS. The decision tree model suggested that age <71 years and adjuvant CT were associated with a better prognosis for GSM patients. The nomogram generated via the Cox proportional hazards model was developed by applying the rms package in R version 3.5.0. The C-index of internal validation for DSS prediction was 0.67 (95% confidence interval (CI), 0.63 to 0.70). The calibration curve at one year suggested that there was good consistency between the predicted DSS and the actual DSS probability. This study was the first to develop a disease-specific nomogram for predicting the prognosis of primary GSM patients after craniotomy, which can help clinicians immediately and accurately predict patient prognosis and conduct further treatment.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Gliosarcoma/diagnóstico , Nomogramas , Factores de Edad , Anciano , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Craneotomía , Femenino , Gliosarcoma/mortalidad , Gliosarcoma/patología , Gliosarcoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Sistema de Registros , Programa de VERF , Análisis de SupervivenciaRESUMEN
Solitary fibrous tumor is one of the most common soft tissue benign tumors that occur in adults, but it rarely occurs in the gastrointestinal tract and even more infrequently occurs in the esophagus. Only 4 cases of esophageal solitary fibrous tumors have been reported in PubMed using the search terms "solitary fibrous tumor" and "esophagus". These cases were all treated using surgical methods. Thus, we report a case of primary solitary fibrous tumor of the esophagus treated by endoscopic submucosal dissection. Endoscopic submucosal dissection was well tolerated in this patient, suggesting that it may be a therapeutic option for primary giant esophageal neoplasms.
Asunto(s)
Disección/métodos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Esofagoscopía/métodos , Tumores Fibrosos Solitarios/patología , Tumores Fibrosos Solitarios/cirugía , Humanos , Masculino , Persona de Mediana EdadRESUMEN
This study aimed to investigate the expression and clinical significance of enoyl coenzyme A hydratase, short chain, 1 (ECHS1), in patients with colorectal cancer (CRC). The ECHS1 protein expression as detected by immunohistochemistry in 148 CRC specimens was evaluated and compared by clinical pathology and prognosis; 38 specimens from proximal non-cancerous colorectal tissues were included as controls. The ECHS1 protein expression was also measured by western blot analysis in 46 fresh CRC tissue specimens and 22 normal colorectal tissue specimens. The rate of positive ECHS1 expression differed significantly between the CRC tissues (56.76%, 84/148) and the proximal non-cancerous colorectal tissues (5.26%, 2/38) (P<0.001). The ECHS1 protein expression was confirmed not to be associated with gender or age. However, the positive expression of ECHS1 tended to be positively associated with clinical TNM stage (P=0.015), lymph node metastasis (P=0.011) and histological differentiation (P=0.028). The expression of the ECHS1 protein on western blot analysis was significantly increased in CRC vs. normal tissues. In addition, the overall survival curves estimated with the Kaplan-Meier method demonstrated that CRC patients exhibiting low ECHS1 expression survived significantly longer compared to patients with high ECHS1 levels (P=0.039). Our data suggested that ECHS1 protein expression may contribute to the occurrence, progression and metastasis of CRC, is closely associated with prognosis and may provide useful information for CRC molecular-targeted therapy.
RESUMEN
AIM: To screen the differential expressed genes in colorectal cancer and polyp tissue samples. METHODS: Tissue specimens containing 16 cases of colorectal adenocarcinoma and colorectal polyp vs normal mucosae were collected and subjected to cDNA microarray and bioinformatical analyses. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm some of the cDNA microarray data. RESULTS: The experimental data showed that eight genes were differentially expressed, most of which were upregulated in adenomatous polyp lesions. Forty-six genes expressions were altered in colorectal cancers, of which 29 were upregulated and 17 downregulated, as compared to the normal mucosae. In addition, 18 genes were similarly altered in both adenomatous polyps and colorectal cancer. qRT-PCR analyses confirmed the cDNA microarray data for four of those 18 genes: MTA1, PDCD4, TSC1 and PDGFRA. CONCLUSION: These differentially expressed genes likely represent biomarkers for early detection of colorectal cancer and may be potential therapeutic targets after confirmed by further studies.