| ObjectiveHepatoblastoma(HB)is the most common malignancy of the liver in children.Current analysis shows that the incidence of hepatoblastoma has increased significantly each year between 2000 and 2015.And with the development of precision surgical techniques,the prognosis for hepatoblastoma is good.However the prognosis of patients with progressive hepatoblastoma remains poor.In recent years,more attention has been paid to the molecular mechanisms of HB and much progress has been made.A better understanding of the molecular mechanisms that lead to hepatoblastoma is essential for early detection and effective treatment.However,the cause and pathogenesis of hepatoblastoma are still unknown,and the ERBB receptor,an RTK receptor that plays a key role in human growth and development,has recently been found to be critically involved in tumour development,yet its relationship with hepatoblastoma remains elusive.Therefore,the aim of this article is to explore the potential relationship between ERBB receptors and hepatoblastoma development.MethodsWe applied immunohistochemical staining to detect the protein expression of ERBB3 in hepatoblastoma tumors and paraneoplastic tissues.To further explore the effect of ERBB3 on the proliferation of hepatoblastoma cells,a lentivirus-mediated short hairpin RNA(shRNA)vector was constructed to stably knock down the ERBB3 gene in hepatoblastoma cell lines HUH6 and HepG2,followed by CCK-8 assay,clone formation assay to explore the effect of ERBB3 on the proliferative capacity of HB cells,and flow cytometry assay to explore the effect of ERBB3 on the apoptosis of HB cells.Then the ERBB3 gene was overexpressed in HepG2 cell line using shRNA and the phenotypic experiments were repeated to reverse the validation.To further investigate the mechanism of ERBB3 gene affecting hepatoblastoma value-added,transcriptome sequencing was performed on ERBB3 knockdown group and control group of hepatoblastoma cell lines,and to understand the signaling pathways involved,the sequencing results were subjected to GO and KEGG analysis to obtain the predicted pathway results,and then the predicted pathway was verified using protein blotting experiments.Results1.In this study,the expression of ERBB3 protein in 45 pairs of hepatoblastoma tumors and paratumoral tissues was detected,and it was found that the expression of VEGF protein in tumor tissues was significantly higher than that in para-tumor tissues.2.In vitro experiments,application of lentiviral vector-mediated short hairpin RNA in hepatoblastoma cell lines(HUH6,HepG2)stably knocked down ERBB3 gene,and ERBB3 expression down-regulated resulted in diminished proliferative capacity and higher number of apoptosis in hepatoblastoma cells.Meanwhile shRNA stably overexpressed ERBB3 gene in HepG2 cell line,and after expression upregulation,the value-added ability was enhanced and apoptosis was reduced.3.The results of cell transcriptome sequencing showed that ERBB3 affected cell proliferation through Ras1/Raf signal pathway.4.It was further verified by immunoblotting that ERBB3 regulated hepatoblastoma cell proliferation and apoptosis through Ras1/Raf signaling pathway.ConclusionERBB3 could be a potential biomarker for early diagnosis of hepatoblastoma and as a new target for molecular therapy of hepatoblastoma.Objective Hepatic mesenchymal tumor is a kind of benign and malignant tumor differentiated from fiber,fat and other mesenchymal cells.Among them,hepatic hamartoma is a kind of benign mesenchymal liver tumor,which can deteriorate into undifferentiated sarcoma of the liver and aggravate the malignant degree of the tumor.Undifferentiated embryonal sarcoma is the highest incidence of primary mesenchymal tumor of the liver,which occurs only in the liver.These two kinds of mesenchymal tumors have the characteristics of rapid growth and large tumor size,but the most effective treatment is still surgical resection.In recent years,with the rise of digital medical technology and the clinical application of three-dimensional visualization of human organs,the accuracy and safety of surgery have been greatly improved.Therefore,this study intends to explore the application value of Hisense computer-assisted surgery system.Methods A total of 8 cases of hepatic mesenchymal tumors were admitted to the Department of Pediatric Surgery at the Affiliated Hospital of Qingdao University from April 2009 to November 2020,including 4 boys and 4 girls;their ages ranged from 10 months to 9years,with a mean age of 4.5 years.In four of the cases,Hisense CAS was used to perform 3D reconstruction of the dynamic enhanced CT images of the upper abdomen to accurately assess the size and location of the tumor and the presence of vascular invasion,determine the possibility of complete resection of the tumor,and make surgical planning.The remaining four cases were operated according to the conventional surgical procedure.All children in this study were treated without preoperative chemotherapy,and the safety and feasibility of applying Hisense CAS was evaluated by combining indicators such as operative time,intraoperative bleeding,survival rate and postoperative follow-up.Results The tumors were resected successfully in 8 cases.during the operation,giant cystic-solid tumors were found to grow extroverted on the surface of the liver,occupying most of the abdominal cavity,with single and intact capsule,located in the right lobe of the liver in 2 cases,the left lobe in 3 cases and the middle lobe in 3 cases.It was quasi-round in 5 cases and irregular in 3 cases.We compared the results of three-dimensional reconstruction with and without three-dimensional reconstruction using Hisense CAS computer-assisted surgery system.Hisense CAS system was used in 4children with preoperative planning,the intraoperative findings were consistent with the results of three-dimensional reconstruction,and the surgical process was highly predictable.The average operation time of 4 children without 3D reconstruction was183.5 ±43.7min,and the average intraoperative blood loss was 52.5 ±36.9ml.The average operation time of 4 cases without 3D reconstruction was about 170 ±46min,and the average blood loss was 37.9 ±41.5m L.All the 8 cases recovered well and survived tumor-free.Conclusion The Hisense Computer Assisted Surgery System(Hisense CAS)provides accurate preoperative assessment of primary mesenchymal tumors of the liver in children,formulates a rational surgical plan,and guides the execution of surgery with real-time precision.The application of Hisense CAS helps to improve the safety and accuracy of liver resection surgery,provides a basis for planning the resection of pediatric liver mesenchymal tumors,and offers the possibility of improving the long-term survival rate of the children. |
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