Protective Effect Of Semaphorin-3A On The Disease-Free Survival After Curative Resection Of HCC

Purpose:To get the knowledge of the tumoral expression of semophorin-3A in liver cancer.To investigate the prognostic value of SEMA3A.To explore the possible mechanism of SEMA3A in tumor as well as in angiogenesis of HCCMaterials and Methods:In the first part,expression of Semaphorin-3A as well as CD34,VEGFA and NRP1 were assessed by immunohistochemistry in tissue microarrays containing liver tissue from 107 patients who had undergone hepatectomy for histologically proven HCC.Prognostic value of these patients and other clinicopathologic factors were evaluated.In the second part,The mRNA concentration of SEMA3A was assessed by RT-PCR method in tissue specimens from 40 patients who had undergone hepatectomy for HCC and the tissue were obtained immediately after the operation.The clinicopathologic factors of these patients were also evaluated.In the last part,18 nude mice(BALB/c male)implanted with live cancer cell were randomly divided into three groups with 6 mice each.These three groups of mice were sacrificed in the 2^rd,4^th and 5^th week respectively,and the tumoral SEMA3A expression was assessed by immunohistochemistry.Results:The SEMA3A IOD value of all the 107 cases patients can be measured out,with an average of 4.23±3.63×10⁶;mRNA level can be measured out by RT-PCR method in all the 40 cases of fresh cancer tissue samples.Tumoral expression of SEAM3A is an independent protective prognostic factor of disease-free survival after curative resection in patients with HCC(rr=0.164-0.887,p=0.025),The 1,3,5-year diseasefree survival rates in patients with high and low SEMA3A exprssion were 85%,71%,71%and 64%,47%,43%respectively(p=0.021).The SEMA3A expression in nude mice implanted with HCC was reduced as the tumoral stage developed and SEMA3A expression in later stage was lower than that in earlier stage p=0.004.SEMA3A expression had a negative correlation-ship with tumor size(r=-0.217,p=0.025).Tumoral SEMA3A expression had a negative correlation tendency with vein invasion and intrahepatic dissemination respectively(r=-0.09,p=0.925;r=-0.23,p=0.812) but without statistical significance.SEMA3A had a negative correlation tendency with tumoral angiogenesis(Microvascular Density,MVD,CD34), and without statistical significance too.High SEMA3A/VEGFA ratio in tumor was correlated with low MVD(r=-0.238,p=0.015),and better disease-free survival p=0.043.There was a significantly positive correlation between the tumoral expression of SEMA3A and VEGFA(r=0.349, p=0.000) Both SEMA3A expression and VEGFA expression are positively correlated with NRP-1(r=0.207,p=0.O33;r=0.186,p=0.054)Conclusion:1.SEMA3A expressed in hepatocellular carcinoma tissue is an independent protective factor of postoperative DFS of HCC 2.SEMA3A may compete with VEGFA in binding NRP1 and suppress angiogenisis in HCC.