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Identification Of Potential Related Genes In Hepatoblastoma Analysis Of Risk Factors For Short-term Postoperative Complications Of Hepatoblastoma

Posted on:2022-05-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:R SunFull Text:PDF
GTID:1484306353958429Subject:Academy of Pediatrics
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PART 1 Identification of potential related genes in hepatoblastomaObjective This study aimed to systematically investigate gene signatures for hepatoblastoma(HB)and identify potential related genes.Materials and Methods GSE131329 and GSE81928 were obtained from the Gene Expression Omnibus database.Differentially expressed genes(DEGs)between hepatoblastoma and normal samples were identified using the Limma package in R.Then,the similarity of network traits between two sets of genes was analyzed by weighted gene correlation network analysis(WGCNA).Cytoscape was used to visualize and select hub genes.PPI network of hub genes was construed by Cytoscape.GO enrichment and KEGG pathway analyses of hub genes were carried out using ClueGO.The pathway of DEGs was analyzed by Cytoscape.The random forest classifier was constructed based on the hub genes using the GSE131329 dataset as the training set,and its reliability was validated using the GSE81928 dataset.The resulting core hub genes were combined with the InnateDB database to identify the innate core genes.We used real-time quantitative PCR to identify the core genes in human hepatoblastoma and normal liver tissues.Results A total of 4244 DEGs in HB were identified.WGCNA identified four modules that were significantly correlated with the disease status.A total of 114 hub genes were obtained within the top 20 genes of each node rank.6982 relation pairs and 3700 nodes were contained in the PPI network of 114 hub genes.GO enrichment and KEGG pathway analyses of hub genes were focused on MAPK,cell cycle,p53,and other crucial pathways involved in HB.A random forest classifier was constructed using the 114 hub genes as feature genes,resulting in a 95.5%true positive rate when classifying HB and normal samples.The classification efficiency of the random forest model was 81.4%.A total of 35 core hub genes were obtained through the mean decrease in accuracy and mean decrease Gini of the random forest model.Finally,10 genes were identified by cross-comparison with the InnateDB database.The expression levels of these 10 genes in hepatoblastoma and normal liver tissues were basically consistent with the database screening.Conclusion Our study established a random forest classifier that identified 10 core genes in HB.These genes may be related to the development of HB.Meanwhile,this study may provide ideas for further study of HB.PART 2 Analysis of risk factors for short-term perioperative complications of hepatoblastomaObjective This study aimed to identify and analyze the risk factors of postoperative complications in children with hepatoblastoma(HB).Materials and Methods The clinical and pathological data of the children who underwent partial hepatectomy in the Department of general surgery and neonatal surgery of Capital Hospital of Pediatrics from May 1,2015 to December 31,2020 were retrospectively reviewed.We used Pearson ?2 test and Logistic regression analysis to analyses the risk factors of perioperative complications in patients with HB.Results 1.There were 277 cases,including 167 males and 110 females,aged from 0.242 to 13 years(median 2 years).93 cases(33.6%)had postoperative complications,including 41 cases of bile leakage,29 cases of pulmonary infection and 24 cases of postoperative bleeding.2.The result of logistic regression analysis showed that there were no significant risk factors for pulmonary infection;3.Eight univariate factors,including PRETERT stage,tumor location,pathological type,resection margin,multiple intrahepatic lesions,vascular invasion,and complications,were significantly associated with postoperative hemorrhage in children with HB;4.The independent risk factors of postoperative complications were the tumor located in the right liver(OR=0.736,95%CI,0.558-0.971,P=0.045),small cell undifferentiated type(OR=2.626,95%CI,1.479-4.665,P=0.048),vascular invasion(OR=0.748,95%CI,0.610-0.917,P=0.036),and complications(OR=1.326,95%CI,1.167-1.506,P=0.047);5.Vascular invasion(OR=0.534,95%CI,0.370-0.769,P=0.01)was an independent risk factor for postoperative bile leakage in children with HB.Conclusion 1.The risk of postoperative complications is higher in children with tumor located in the right liver,pathological type of small cell undifferentiated,vascular invasion and preoperative complications.2.The risk of postoperative bile leakage is higher in children with vascular invasion.3.Postoperative bleeding may be related to PRETEXT stage,tumor location,pathological type,resection margin,multiple intrahepatic lesions,vascular invasion,and preoperative complications.
Keywords/Search Tags:Hepatoblastoma, Gene expression omnibus, Random forest classifier, Nomogram, Diagnosis, Surgery, Complication, Bile leakage, Risk factors
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