Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. However, the mechanistic relationships among various genes and signaling pathways are still largely unclear. In this study, we aimed to elucidate potential core candidate genes and pathways in HCC. The expression profiles GSE14520, GSE25097, GSE29721, and GSE62232, which cover 606 tumor and 550 nontumour samples, were downloaded from the Gene Expression Omnibus (GEO) database. Furthermore, HCC RNA-seq datasets were also downloaded from the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were filtered using R software, and we performed gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using the online databases DAVID 6.8 and KOBAS 3.0. Furthermore, the protein-protein interaction (PPI) network complex of these DEGs was constructed by Cytoscape software, the molecular complex detection (MCODE) plug-in and the online database STRING. First, a total of 173 DEGs (41 upregulated and 132 downregulated) were identified that were aberrantly expressed in both the GEO and TCGA datasets. Second, GO analysis revealed that most of the DEGs were significantly enriched in extracellular exosomes, cytosol, extracellular region, and extracellular space. Signaling pathway analysis indicated that the DEGs had common pathways in metabolism-related pathways, cell cycle, and biological oxidations. Third, 146 nodes were identified from the DEG PPI network complex, and two important modules with a high degree were detected using the MCODE plug-in. In addition, 10 core genes were identified, TOP2A, NDC80, FOXM1, HMMR, KNTC1, PTTG1, FEN1, RFC4, SMC4, and PRC1. Finally, Kaplan-Meier analysis of overall survival and correlation analysis were applied to these genes. The abovementioned findings indicate that the identified core genes and pathways in this bioinformatics analysis could significantly enrich our understanding of the development and recurrence of HCC; furthermore, these candidate genes and pathways could be therapeutic targets for HCC treatment. K E Y W O R D S bioinformatical analysis, differentially expressed genes (DEGs), hepatocellular carcinoma (HCC), pathways J Cell Biochem. 2019;120:10069-10081.wileyonlinelibrary.com/journal/jcb

The current clinical classification of primary liver cancer is unable to efficiently predict the prognosis of combined hepatocellular cholangiocarcinoma (cHCC). Accurate satellite nodules (SAT) and microvascular invasion (MVI) prediction in cHCC patients is very important for treatment decision making and prognostic evaluation. The aim of this work was to explore important factors affecting the prognosis of cHCC patients after liver resection and to develop preoperative nomograms to predict SAT and MVI in cHCC patients. The nomogram was developed using the data from 148 patients who underwent liver resection for cHCC patients at our hospital between January 2006 and December 2014. Based on the results of the multivariate analysis, a nomogram integrating all significant independent factors affecting overall survival and recurrence-free survival was constructed to predict the prognosis of cHCC. Next, risk factors for SAT and MVI were evaluated with logistic regression. Blood signatures were established using the LASSO regression, and then, we combined the clinical risk factors and blood signatures of the patients to establish predictive models for SAT and MVI. The C-index of the nomogram for predicting survival was 0.685 (95% CI, 0.638 to 0.732), which was significantly higher than the C-index for other liver cancer classification systems.

Background: Hepatic alveolar echinococcosis (HAE) lesions with inferior vena cava (IVC) invasion require combined resection of the liver and IVC. The outcomes of different surgical treatments, including in situ, ante situm and ex vivo resection, remain unclear.Methods: A total of 71 consecutive HAE patients who underwent hepatectomy with retrohepatic IVC resection were included. The patients were divided into ex vivo liver resection and autotransplantation (ERAT) group (n = 45) and in vivo resection group (n = 26). These techniques were assessed for feasibility and short-and long-term outcomes.Results: There were no significant differences with respect to postoperative complications and mortality between the ERAT and in vivo resection groups. The causes of mortality were liver failure in 3 patients, hemorrhagic shock in 1 patient, intra-abdominal bleeding in 1 patient, and acute cerebral hemorrhage in 1 patient. During a median of 22 months followed-up time, 2 patients developed ascites because of venous outflow stenosis, and 1 patient developed biliary stenosis in the ERAT group. The distant metastasis, local recurrence, and mortality rates were 0%, 1.4%, and 8.5%, respectively. Conclusion:Combined liver resection and reconstruction of the IVC can be safely performed in selected patients with in situ, ante situm, and ex vivo resection.

Objective: To evaluate the benefit and safety of preoperative administration of steroid in patients undergoing liver resection. Methods: Randomized controlled trials (RCTs) which comparing preoperative administration of steroid in patients undergoing liver resection with control group were identified through a systematic literature search in PubMed, Embase, and Cochrane Library Central databases. This meta-analysis was carried out to assess the liver function, inflammatory response, and postoperative complications after liver surgery. Results: Six RCTs including 411 patients were reviewed. The pooled result showed that there was no significant difference in the incidence of overall complications between the steroid group and the control group (OR, 0.57; 95% CI, 0.27–1.17; P = 0.13). With respect to specific complications, no significant difference was detected between the two groups in infection complications (OR, 0.95; 95% CI, 0.13–6.95; P = 0.96), wound complications (OR, 0.65; 95% CI, 0.32–1.33; P = 0.24), liver failure (OR, 0.41; 95% CI, 0.10–1.64; P = 0.21), bile leakage (OR, 0.57; 95% CI, 0.17–1.89; P = 0.36), and pleural effusion (OR, 1.24; 95% CI, 0.55–2.78; P = 0.60). For liver function, the level of serum total bilirubin (TB) on postoperative day 1 (POD 1) was significantly decreased associated with the intervention of steroid (MD, −0.54; 95% CI, −0.94 to −0.15; P = 0.007). However, no significant difference was found in the level of alanine aminotransferase (ALT) (MD, −69.39; 95% CI, −226.52 to 87.75; P = 0.39) and aspartate aminotransferase (AST) (MD, −93.44; 95% CI, −275.68 to 88.80; P = 0.31) on POD 1 between the two groups. Serum IL-6 level on POD 1 (MD, −57.98; 95% CI, −73.04 to −42.91; P < 0.00001) and CRP level on POD 3 (MD, −4.83; 95% CI, −6.07 to −3.59; P < 0.00001) were significantly reduced in the steroid group comparing to the control group. Compared with the control group, the level of early postoperative IL-10 was significant higher in the steroid group (MD, 17.89; 95% CI, 3.89 to 31.89; P = 0.01). Conclusion: Preoperative administration of steroid in liver resection can promote the recovery of liver function and inhibit the inflammatory response without increasing postoperative complications. Further studies should focus on determining which patients would benefit most from the steroid.

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