| Part I Analysis of clinicopathological features and prognosis of 98 cases of small hepatocellular carcinoma[Objective]To analyze the clinicopathological features and prognosis of patients of small hepatocellular carcinoma.[Methods]The clinicopathological data and follow-up data of 98 patients with small hepatocellular carcinoma who underwent RO resection from January 2009 to December 2013 were retrospectively analyzed.[Results]All of the patients were followed up.The 1-year,3-year and 5-year overall survival rates were 99.0%,91.7%,and 76.3%,respectively.The median overall survival time(OS)was 52 months.The progression-free survival rates were 86.7%,66.2%and 55.0%,respectively,and the median disease-free survival time(DFS)was 43.5 months.Univariate analysis showed that satellite nodules,liver capsule invasion and postoperative recurrence were associated with OS(P<0.05).Long-term drinking,satellite nodules and liver capsule invasion were associated with DFS(P<0.05).Multivariate analysis showed that long-term drinking was an independent factor influencing the disease-free survival time of small hepatocellular carcinoma(P = 0.003).Postoperative recurrence time and liver capsule invasion were independent factors affecting the overall survival time of small hepatocellular carcinoma(all P<0.05).All 98 cases were then divided into two groups with long-term drinking and without long-term drinking.Further analysis revealed that preoperative rise in ALT was a significant adverse prognostic factor of postoperative disease-free survival and overall survival for without long-term drinking group.For long-term drinking group,satellite nodule may be a significant adverse factor for the overall survival time and disease-free survival time.Multivariate analysis showed that postoperative recurrence time was an independent risk factor for the overall survival time(P<0.05).[Conclusion]For the treatment of small hepatocellular carcinoma,under the premise of the R0 removal of tumor,minimizing the scope of resection of normal liver could protect liver function.Postoperative recurrence time within 2 years suggests a poor prognosis.Long-term drinking can promote the recurrence of small hepatocellular carcinoma.For patients without long-term drinking,elevated preoperative ALT can affect postoperative recurrence of small hepatocellular carcinoma.Part Ⅱ.Differences in gene expression profiles of peripheral blood leukocytes between multifocal and single hepatocellular carcinoma[Objective]Multifocal and single hepatocellular carcinoma are heterogeneous diseases with different clinical manifestations and molecular biology characteristics.The study are to explore the different molecular events of peripheral blood leukocytes of multifocal and single lesions and to analyze the difference of microenvironment of multifocal and single hepatocellular carcinoma.[Methods]In this study,15 patients with single hepatocellular carcinoma and 9 patients with multifocal hepatocellular carcinoma were recruited.The expression profile of peripheral blood mononuclear cells was detected by Agilent 4*44k gene chip platform to get differentially expressed genes.[Results]592 differentially expressed genes were found in peripheral blood mononuclear cells of multifocal and single hepatocellular carcinoma by expression profiling.Principal component analysis showed that there was a significant difference in the expression profile of peripheral blood leukocyte gene between patients with multifocal liver cancer and single liver cancer.GO enrichment analysis showed that 536 up-regulated differential expression genes involved in the biological processes include:cytokine-mediated immune response,intercellular signal transduction,injury repair response,p38MAPK signaling pathway positive regulation,immune system process regulation and the formation of the nervous system and synapses.The biological processes involved in the down-regulation of 56 genes mainly include the transcription process and regulation of DNA,the biosynthesis of ribosomes and the synthesis of collagen fibers.Pathway analysis showed that the differentially expressed genes were mainly associated with the following pathways:tyrosine metabolic processes,neurotrophic ligand-receptor interactions,cell tight junction processes,serotonin synapses,and mineral uptake signaling pathways Related.Samples GSVA analysis showed that a total of 339 genes(p<0.05)were screened for comparison with peripheral blood leukocytes in patients with multifocal liver cancer,which mainly involved:functional regulation of various immune cells(CD4 T cells,DC,TGF-P,IL-1,IL-6,IFN,HIF,etc.),regulation of MAPK signaling pathway,and lipid metabolism in tumor microenvironment homeostasis and lipid synthesis regulation.[Conclusion)There were significant differences in the gene expression profiles of peripheral blood leukocytes in patients between multifocal and single hepatocellular carcinoma.The expression of TGF-β signaling pathway,liposome synthesis process and HIF gene expression in patients with multifocal hepatocellular carcinoma were significantly higher than those in single hepatocellular carcinoma.The p38/MAPK signaling pathway was down-regulated in the gene expression profile of multifocal patients.There are more up-regulated genes in the tumor microenvironment of multifocal hepatocellular carcinoma. |
