| Objective:(1)To investigate the correlation between the gene polymorphism of Axon guidance pathway(PLXNC1、ITGβ1、RAC1) and genetic susceptibility of hepatocellular carcinoma (HCC) in Guangxi;(2)To investigate the protein expression of PLXNC1、ITGβ1、KRAC1 and SEMA7A in hepatocellular carcinoma.Methods(1) Screen function single nucleotide polymorphism (SNP) site of genes(PLXNC1、ITGβ1、RAC1) in axon guidance pathway polymorphism by Bioinfromatic techniques;Genotype and alleles of the PLXNC1、ITGβ1 and RACl’s function SNP were determined in 20 liver cancer family groups(79 patients) and 10 normal control groups(40 patients) in Fusui county using Time of Flight Mass Spectrometer (TOF). The people classified into three group:patients of HCC families named A group, Non-patients of HCC families named B group,Normal control families named C group.(2)The protein expression level of PLXNC1,ITGβ1、SEMA7A、RAC1 was detected in 50 cases with Hepatocellular Carcercerous tissues,50 cases with Hepatocellular Paracarcercerous tissues,40 cases with Bening Hepatocellular Lesions tissues by immunohistochemistry (SP).Results(1) DPLXNC1 (rs2272335)JTGβ1(rs22298141) and RAC1(rs 6951997) maybe the functional SNP site with the risk of HCC;(2) For the Alleles of PLXNC1 (rs2272335) site,the risk of HCC for people with C was 0.47 times (95%CI=0.1-2.2,P=0.053) that of people with T in the members of B group, the risk of HCC for people with C was 4.16 times (95%CI=0.37-47.3,P=0.032) that of people with T in the members of C group; the frequencies of C in the members of (A+B) group was 7.6 times (P=0.04 <.05,OR=7.6,95%CI:0.99-59.50)that of C group; After corrected sex, age, smoke, drinking, HBsAg, the frequencies of C in the members of (A+B) group was 5.09 times (P=0.03<0.05,OR=5.09,95%CI:0.62-41.60)that of C group.For the genotype of PLXNC1 (rs2272335) site, the risk of HCC for people with TC was 0.68 times that of people with TT(95% CI=0.13-3.52,P=0.65) in the members of B group, the risk of HCC for people with TC was 4.3 times that of people with TT(95% CI=0.37-50.95,P=0.24) in the members of B group, the frequencies of TC in the members of (A+B) group was 5.82 times (P=0.10 >0.05,95%CI:0.72-47.21)that of C group; After corrected sex、age、smoke、 drinking、HBsAg, the frequencies of TC in the members of (A+B) group was 4.68 times (95%CI:0.54-40.17,P=0.15>0.05)that of C group.(3)For the Alleles of ITG(31(rs22298141)site,the risk of HCC for people with G was 0.67 times (95%CI=0.31-1.45,P=0.31) that of people with A in the members of B group, the risk of HCC for people with G was 0.75 times (95%CI=0.33-1.7,P=0.50) that of people with A in the members of C group; the frequencies of the A and G alleles were similar in (A+B) group and C group (P>0.05).For the genotype of ITGβ1(rs2298141) site, the risk of HCC for people with AG, GG was 0.91,2.2 times that of people with AA separately(95% CI=0.31-2.71,P=0.86;95% CI=0.40-11.96.45,P=0.37) in the members of B group. the risk of HCC for people with AG,GG was 0.67,1.05 times that of people with AA separately(95% CI=0.22-2.1,P=0.50;95% CI= 0.17-6.6,P=0.96) in the members of C group;the frequencies of the AG and GG genotype were similar in (A+B) group and C group (P>0.05);(4)For the Alleles of RAC1 (rs 6951997)site,the risk of HCC for people with G was 0.73 times (95%CI=0.08-6.7,P=0.78) that of people with T in the members of B group 。the risk of HCC for people with G was 0.49 times (95%CI=0.30-8.1,P=0.62) that of people with T in the members of C group.the frequencies of the G and T alleles were similar in (A+B) group and C group (P>0.05).For the genotype of RAC1 (rs 6951997) site, the risk of HCC for people with GT was 0.72 times that of people with TT (95% CI=0.08-6.9,P=0.78) in the members of B group.the risk of HCC for people with GT was 0.72 times that of people with TT(95% CI=0.12-34.63,P=0.62)in the members of C group;the frequencies of the AG and GG genotype were similar in (A+B) group and C group (P>0.05).(5)The expression level of PLXNC1 protein in Hepatocellular Carcercerous tissues(3.12 ±1.12)was significantly higher than that in Hepatocellular Paracarcercerous tissues (1.54±0.67)and Bening Hepatocellular Lesions tissues(1.23±0.87) (P＜0.05), but there was no significant difference between Hepatocellular Paracarcercerous tissues and Bening Hepatocellular Lesions tissues(P>0.05).(6)The expression level of ITGβ1 protein in Hepatocellular Carcercerous tissues(3.45±1.25) was significantly higher than that in Hepatocellular Paracarcercerous tissues (1.76±0.98) and Bening Hepatocellular Lesions tissues(1.02±0.56)(P<0.05), the expression level of ITGβ1 protein in Hepatocellular Paracarcercerous tissues was significantly higher than that in Bening Hepatocellular Lesions tissues (P< 0.05);(7)The expression level of SEMA7A protein in Hepatocellular Carcercerous tissues(3.03±1.07)was significantly higher than that in Hepatocellular Paracarcercerous tissues(1.47±0.58) and Bening Hepatocellular Lesions tissues(1.17±0.92) (P＜0.05), but there was no significant difference between Hepatocellular Paracarcercerous tissues and Bening Hepatocellular Lesions tissues (P>0.05);(8)The expression level of RAC1 protein in Hepatocellular Carcercerous tissues (3.25±1.14) was significantly higher than that in Hepatocellular Paracarcercerous tissues (1.68±0.87) and Bening Hepatocellular Lesions tissues(0.92±0.67)(P<0.05), the expression level of RAC1 protein in Hepatocellular Paracarcercerous tissues was significantly higher than that in Bening Hepatocellular Lesions tissues(P<0.05);(9)The expression level of PLXNC1、ITGβ 1、SEMA7A, RAC1 protein in liver cancer tissues had no significant correlations with the sex,age, size of the primary cancer, HBsAg, AFP;Conclusion(1) The PLXNC1 (rs2272335) site may be associated with genetic susceptibility of HCC in Guangxi, zhuan population;the ITGβ1(rs2298141) polymophism may not be associated with genetic susceptibility of HCC in Guangxi, zhuan population;the RAC1 rs 6951997 polymophism may not be associated with family clustering genetic susceptibility of HCC in Guangxi, zhuan population;(2)the Axon guidance pathway of SEMA7A-ITGβ1-PLXNC1and gene(PLXNC1,ITGβ1、RAC1' SEMA7A) protein expressed maybe having the correlations with the genetic susceptibility of HCC in guangxi. |
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