[Genotype-phenotype relationship and genetics study of 115 cases with Wilson's disease].

Objective: To explore the genotype-phenotype relationship of Wilson's disease (WD) and further study the mutation spectrum in the ATP7B gene. Methods: The clinical data and genetic test results of 115 cases with WD diagnosed in the First Affiliated Hospital of Zhengzhou University from 2015 to 2022 were retrospectively analyzed. The rank sum test was used for quantitative data comparison, and χ(2) test was used for count data comparison. Multivariate logistic regression was used to analyze the relationship between patients' genotype and phenotype. Results: The onset of liver manifestations (hepatic type) accounted for 60.9%, neurological symptoms (cerebral type) for 13.0%, and mixed hepato-cerebral symptoms for 26.1%. Presymptomatic individuals (hepatic types) accounted for 62.9%. Next-generation sequencing- diagnosed WD cases accounted for 87.8%. Combined multiplex ligation-dependent probe amplification assay-diagnosed WD cases accounted for 89.6%. A single case with a detected pathogenic locus accounted for 10.4%. The diagnostic rate of WD by genetic testing combined with clinical data was 100%. A total of 76 ATP7B mutations were detected, and the top three mutation frequencies were c.2333G>T (p.Arg778Leu) (30.7%), c.2975C>T (p.Pro992Leu) (7.3%), and c.2621C>T (p.Ala874Val) (6.4%). The mutations were mainly distributed in exons 8, 11-13, and 15-18, accounting for more than 90% of the total mutations. Eight new mutations were found, including c.3724G>A (p.Glu1242Lys), c.3703G>C (p.Gly1235Arg), c.3593T>C (p.Val1198Ala), c.2494A>C (p.Lys832Gln), c.1517T>A (p.Ile506Lys), c.484G>T (p.Glu162Ter), c.1870-49A>G, and the missing of exons 10-21. Liver histopathology showed cellular edema, degeneration, inflammation, and necrosis, as well as a 42.8% copper staining positive rate. Genotype-phenotype analysis showed that the p.Arg778Leu mutation had higher alanine aminotransferase (ALT) levels than those carrying other mutations (P=0.024), while the homozygous mutation of p.Arg778Leu was associated with cerebral-type patients (P=0.027). Conclusion: Genetic testing plays an important role in the diagnosis of WD. p.Arg778Leu is the first high-frequency mutation in the Chinese population, and patients carrying it have higher ALT levels. The p.Arg778Leu homozygous mutation is prone to causing cerebral-type WD. This study expands the ATP7B gene mutation spectrum.

Increased expression of vascular endothelial growth factor in hepatocellular carcinoma after transcatheter arterial chemoembolization.

BACKGROUND: Changes in the biological behavior of residual viable hepatocellular carcinoma (HCC) tissue after transcatheter arterial chemoembolization (TACE) remain unclear. Several studies have reported that TACE inhibits tumor angiogenesis and induces tumor cell apoptosis, while other studies have found that TACE stimulates tumor angiogenesis and thus increases the proliferative activity of the tumor cells to some degree. PURPOSE: To investigate the intratumoral microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in residual surviving cancerous tissue after TACE in HCC. MATERIAL AND METHODS: Tumor specimens from 63 histopathologically diagnosed patients were studied: 42 comprising the control group (treated by surgery alone) and 21 comprising the TACE group (those treated by TACE 1-2 times prior to surgical resection). The number of VEGF-positive cells, MVD, and microvessel diameter were measured. RESULTS: The MVD was 51.69+/-18.17 and 58.57+/-15.75 in the control and TACE groups, respectively. There was no significant difference between the two groups (t=1.48, P>0.05). The microvessel diameter was 17.62+/-10.54 microm and 15.79+/-7.65 microm in the control and TACE groups, respectively, indicating no significant difference between the two groups (t=0.71, P>0.05). The number of VEGF-positive cells in the TACE group, i.e., 243.66+/-88.88, was higher than that in the control group, i.e., 138.26+/-65.24 (t=5.34, P<0.01). TACE increased VEGF expression in the residual surviving HCC tissues, and there was a positive correlation between VEGF expression and MVD (r=0.4936, t=4.4329, P<0.05) in the HCC tissue. CONCLUSION: The study indicates that the residual surviving cancerous tissue in HCC after TACE has a rich vascularity. TACE increases VEGF expression in the residual surviving cancerous tissue.