ABSTRACT
Objective To investigate the expression level and clinical significance of ALDH5A1 in ovarian cancer (OC) tissues, as well as to explore the possible mechanism associated with the invasion and migration of OC cells. Methods We initially compared ALDH5A1 expression in metastatic tissues and the primary site of OC based on the GEO database. Then, wound-healing and Transwell assays were utilized to determine the biological role of OC cells transfected with ALDH5A1 siRNA. To unravel the potential mechanism of ALDH5A1 meditating the metastasis of OC, the coexpression profile of ALDH5A1 in OC cell lines and OC patients were generated using cBioPortal. Moreover, the TCGA and GEO databases were used to analyze the relationship between ALDH5A1 expression and the prognosis of OC patients. The HPA database was further used to confirm the relative expression of ALDH5A1 and MMPs in OC patients. Results ALDH5A1 expression was downregulated in metastatic tissues compared with the primary site of OC, and ALDH5A1 knockdown promoted the malignant behavior of OC cells. Additionally, the coexpression profile of ALDH5A1 was significantly enriched in the extracellular matrix (ECM) organization pathway. Western blot assay further confirmed that the expression of MMP, which played an important role in the ECM pathway, was negatively correlated with ALDH5A1 expression in OC. These results indicated that ALDH5A1 may participate in the metastasis and invasion of OC via the ECM organization pathway. Finally, KM survival plots revealed that the survival rates of OC patients with lower ALDH5A1 expression were obviously lower. Conclusion ALDH5A1 downregulation may promote the tumor metastasis and contribute to poor prognosis in OC.
ABSTRACT
Objective To study the clinical and laboratory diagnosis and follow-up of 4-hydroxy butyrate aciduria in children.Methods From June 2012 to July 2017,9 cases in Tianjin Children's Hospital were analyzed.According to their clinical features,multidimensional analysis was pedormed by using head magnetic resonance imaging (MRI),urine gas chromatography-mass spectrometry (GC/MS) semi-quantitative testing and gene mutation analysis of ALDH5A1.Results The onset age of the 9 cases was less than 1 year old,and all had psychomotor retardation,in which 4 cases with epileptic seizures,1 case with consciousness disturbance and 1 case with involuntary movement.All the cases underwent head MRI and 4 cases showed bilateral symmetry pallidal lesions,including 1 case with symmetry abnormality of the midbrain cerebral peduncle,1 case with encephalomalacia in left temporal cortex and 4 cases with widening of the ventricle and extracerebral space.By the urine GC/MS semi-quantitative testing,all 9 the cases showed increasing 4-hydroxy butyric acid and by the ALDH5A1 gene mutation analysis,all 9 the cases were detected with gene mutation (3 cases belonging to c.1568C ＞ T homozygous mutation,1 case belonging to c.839T ＞ G homozygous mutation and the other 5 cases belonging to compound heterozygous mutation,which included c.691G ＞ A,c.1568C ＞T;c.1383_2delA,c.1568C ＞ T;c.527G ＞ A,c.691G ＞ A;c.904G ＞ A,c.1022C ＞ A;c.398_399delA,c.638G ＞ T).Nine cases were given symptomatic treatment,and 4 cases with epileptic seizures were given antiepileptic drugs.During the follow-up of the above 9 cases,1 case died of status epilepticus,1 case had been under control for 5 years,and 2 cases were effectively treated.Psychomotor retardation was improved in varying degrees in 8 cases.Involuntarymovement disappeared in 1 case while 2 cases still showed increasing 4-hydroxy butyric acid by means of urine GC/MS semi-quantitative testing.Conclusions Most of 4-hydroxy butyrate aciduria occurs within 1 year old,with psychomotor development as the first manifestation,which can be associated with epilepsy.The head MRI is characterized by a symmetrical Globus pallid abnormal signal.Urine GC/MS shows an increase in 4-hydroxy butyrate,which is the basis for biochemical diagnosis of the disease.Its accumulation in the body mainly damages the central nervous system.ALDH5A1 is a disease-causing gene,in which c.1568C ＞ T site has a high mutation frequency,and it is speculated that this site may be a hot spot mutation in Chinese children.Patients with epilepsy may die from status epilepticus and may be used as a clinical indicator to judge the severity of the disease.There is no specific treatment,and the patients combined with epilepsy can be treated with anti-epileptic drugs.Valproic acid should be avoided as it can aggravate the condition.
ABSTRACT
Objective@#To study the clinical and laboratory diagnosis and follow-up of 4-hydroxy butyrate aciduria in children.@*Methods@#From June 2012 to July 2017, 9 cases in Tianjin Children′s Hospital were analyzed.According to their clinical features, multidimensional analysis was performed by using head magnetic resonance imaging (MRI), urine gas chromatography-mass spectrometry (GC/MS) semi-quantitative testing and gene mutation analysis of ALDH5A1.@*Results@#The onset age of the 9 cases was less than 1 year old, and all had psychomotor retardation, in which 4 cases with epileptic seizures, 1 case with consciousness disturbance and 1 case with involuntary movement.All the cases underwent head MRI and 4 cases showed bilateral symmetry pallidal lesions, including 1 case with symmetry abnormality of the midbrain cerebral peduncle, 1 case with encephalomalacia in left temporal cortex and 4 cases with widening of the ventricle and extracerebral space.By the urine GC/MS semi-quantitative testing, all 9 the cases showed increasing 4-hydroxy butyric acid and by the ALDH5A1 gene mutation analysis, all 9 the cases were detected with gene mutation (3 cases belonging to c. 1568C>T homozygous mutation, 1 case belonging to c. 839T>G homozygous mutation and the other 5 cases belonging to compound heterozygous mutation, which included c. 691G>A, c.1568C>T; c.1383_2delA, c.1568C>T; c.527G>A, c.691G>A; c.904G>A, c.1022C>A; c.398_399delA, c.638G>T). Nine cases were given symptomatic treatment, and 4 cases with epileptic seizures were given antiepileptic drugs.During the follow-up of the above 9 cases, 1 case died of status epilepticus, 1 case had been under control for 5 years, and 2 cases were effectively treated.Psychomotor retardation was improved in varying degrees in 8 cases.Involuntary movement disappeared in 1 case while 2 cases still showed increasing 4-hydroxy butyric acid by means of urine GC/MS semi-quantitative testing.@*Conclusions@#Most of 4-hydroxy butyrate aciduria occurs within 1 year old, with psychomotor development as the first manifestation, which can be associated with epilepsy.The head MRI is characte-rized by a symmetrical Globus pallid abnormal signal.Urine GC/MS shows an increase in 4-hydroxy butyrate, which is the basis for biochemical diagnosis of the disease.Its accumulation in the body mainly damages the central nervous system.ALDH5A1 is a disease-causing gene, in which c. 1568C>T site has a high mutation frequency, and it is speculated that this site may be a hot spot mutation in Chinese children.Patients with epilepsy may die from status epilepticus and may be used as a clinical indicator to judge the severity of the disease.There is no specific treatment, and the patients combined with epilepsy can be treated with anti-epileptic drugs.Valproic acid should be avoided as it can aggravate the condition.