A Pilot Study Of The Clinical Significance Of The Vasculogenic Mimicry Expression And The Formation Mechanism In Primary Liver Cancer

Objeetive：1、To explore whether vasculogenic mimicry(VM)exists in Primary livercancer(PLC). Explore the relationship between VM and clinicopathologicalparameters and prognosis of primary liver cancer Patients.2、Detection the expression of Hif-1αand Epha2 in Primary liver cancer.Explore the relationship between Hif-1α/Epha2 and VM , and further toinvestigate the potential mechanism of VM.Methods：The complete clinical and pathological data of 161 PLC cases werecollected in this study. The expression of VM were observed byimmunohistochemical double staining of CD34 and PAS; And detected theexpression of Hif-1α,Epha2 proteins by immnohistochemistrial staining. Toanalyze the expression of VM according to the clinicopathologic Parameterand the expression of Hif-1α, Epha2.Results：1、The positive rates of VM in primary liver cancer and control groupsrespectively 37.9%; 0%, the difference was higher statistically significant(P=0.001).2、The relationship between VM and the clinicopathological factorsThe expression of VM was positively correlated with clinical stage, tumor size, HCC Edmondson stage (P=0.025,0.032,0.006); The expression ofVM was significantly upregulated in PLC with cirrhosis (χ~2=8.284,P=0.004);The expression of VM in different pathological types of PLC has nosignificant difference (χ~2=2.269,P=0.337); There was no significantcorrelation of VM and the PLC with HBsAg positive (χ~2=0.029,P=0.865);Logistic regression model for multivariate analysis showed: cirrhosis, clinicalstage is the independent factors of the expression of VM in primary livercancer (P=0.007; P=0.041).3、The expression of Hif-1αand Epha2The positive rate of Hif-1αwas 65.8% (106/161),the VM group,positiverate of Hif-1α(+~ + + +) was 75.4%,and non-VM group,positive rate ofHif-1α(+~ + + +) was 60.0%,and the difference was statistically significant(χ~2=10.608,P=0.014).The positive rate of Epha2 was 69.6% (106/161),theVM group,positive rate of Epha2 (+~ + + +) was 80.3%,and non-VM group,positive rate of Epha2 (+~ + + +) was 63.0%,and the difference wasstatistically significant (χ~2=8.490,P=0.037).The Spearman law analysissuggests that Epha2 and Hif-1αboth in primary hepatocellular expression wassignificantly correlated (r=0.194, P=0.014). There were statisticallysignificant of the expression of Epha2/Hif-1αand PLC with cirrhosis,clinicalstage, tumor size (p＜0.05).4、Survival analysis and COX regression analysisThe results of life-table showed that VM group and non-VM group had1-, 3- and 5-year survival rates were 56%/79%,26%/49%,26%/46%.Kaplan-Meier survival analysis the survival rate of the two groups, ParallelLog-rank test, and the difference was statistically significant(Log-Rank=10.705,P=0.001).Similarly, There were statistically significant of the survival analysis of Epha2/Hif-1α（Log-rank =4.143，P=0.042；Log-rank=9.923，P=0.002）. Cox regression displayed VM expression, the expressionof Epha2,pathological type of PLC were significant independence factorswhich can effect the Prognosis of the long-term survival rate of PLC（P＜0.05）.Conclusion：1、Vasculogenic mimicry exists in Primary liver cancer.2、The later TNM stage of PLC, the higher pathological grade (the lowerdegree of cell differentiation) lead to a higher expressive ability of VM;andPLC with cirrhosis of the liver can increase the VM expression. The differentPLC pathological type has nothing to do with VM expression.3、The expression of Hif-1αand Epha2 in primary liver cancer waspositively correlated with the VM. PLC with cirrhosis can significantlyup-regulated the expression of Hif-1α, and Hif-1αregulates the downstreamgene, causing Epha2 overexpression, which led to the VM expression inprimary liver cancer. Hif-1αand Epha2 were important regulatory factor inThe formation of the VM.4、The VM group survival time is shorter than the non-VM group; It hascertain significance of Joint detection VM, Hif-1αand Epha2 on evaluationthe prognosis of primary liver cancer.