| Objective: Wnt signaling pathway is a evolutionary conservativesignaling pathway and has highly homology from lower organisms to highermammals,which controls cell proliferation, differentiation and apoptosis, and play animportant role in embryogenesis and many types of cell fate determination.Wnt pathway disorder is involved in the occurrence and development ofvarious of body malignant tumors. Especially classical wnt/β-catenin signalingpathways is related to the occurrence and development of HCC.In this study, the immunohistochemical staining was used to study theexpression characteristics of Wnt-1, β-catenin and Axin-1in HCC tissue,non-cancerous cirrhosis hepatic tissue and normal hepatic tissue, to furtherexplore the clinical significance of Wnt/β-catenin signal pathway.Methods:1、Samples collection:50specimens of HCC,50specimens of adjacentnon-cancerous cirrhosis hepatic tissue and7specimens of normal hepatictissue were obtained from the fourth hospital of Hebei Medical Universitywithout clinical treatment before operation.2、Imunostaining:The samples were fixed by10%formaldehyde, embededin paraffin after excision. The immunohistochemical staining was used todetect differences of the expression Wnt-1, β-catenin and Axin-1in HCCtissue, non-cancerous cirrhosis hepatic tissue and normal hepatic tissue， toanalysis of the relation between the expression of protein and the clinicalmanifestations, and understand whether the difference of expression willinfluence prognosis of patient by follow-up for the survival condition.Resluts:1、Survival analysis of the clinical and pathological data in postoperative HCC patients: Age, sex, the size of tumor and HBsAg were no statisticaldifference in postoperative HCC patients. The clinical stage（Ⅰb+Ⅱa stage,Ⅱb+Ⅲa stage）(χ2=14.951，P=0.000), Pathological classification（χ2=19.937，P=0.000）, AFP（χ2=13.808，P=0.000）, HBeAb（χ2=9.907，P=0.002）and the portal vein tumor thrombosis or distant metastasis（χ2=19.381，P=0.000）were the significant prognostic factors in postoperative HCCpatients. The patients in the earlier clinical stages, high pathologicalclassification, lower AFP(≤400ng/ml), HBeAb negative and without portaltumor bolts or the distant metastasis, had the higher survival rate, whose meansurvival time was longer, the prognosis was better.2、Wnt-1protein wasn’t expressed, or a few in the cell membrane andcytoplasmic of the normal liver tissue， which showed by light yellowgranular. Wnt-1protein was expressed in the cell membrane and cytoplasm ofa few of adjacent non-cancerous hepatic tissue, which showed by light yellowor yellow Scattered floe. While Wnt-1protein was expressed in the cellmembrane and cytoplasm of most of in the liver cancerous organization whichshowed by continuous yellow or brown crumb. The expression of Wnt-1protein hadn’t significant difference between in adjacent non-canceroushepatic tissue and in normal hepatic tissue（Z=-0.560，P=0.567）. Statisticaldifference existed between in normal hepatic tissue and in HCC tissue（Z=-3.110，P=0.002）and also existed between in adjacent non-canceroushepatic tissue and in HCC tissue （Z=-5.635，P=0.0000）. The expression ofWnt-1hadn’t significant difference in sex, HbsAg, AFP, the size of tumor andthe portal vein tumor thrombosis or distant metastasis. The expression ofWnt-1was higher in HCC patients with HBeAb negative. The display ofWnt-1was ierrelevant with the clinical stage and pathological classification ofHCC patients. The expression of Wnt-1was relevant with the prognosis ofpatients. The patients with negative expression of Wnt-1, their6monthssurvival rate was100%,12months survival rate was100%,24monthssurvival rate was50%, the mean survival time was30.3months. The patientswith weak positive expression of Wnt-1, their6months survival rate was 100%,12months survival rate was57.1%,24months survival rate was7.1%,the mean survival time was14.9months. The patients with positive expressionof Wnt-1, their6months survival rate was68.8%,12months survival rate was31.2%,24months survival rate was6.2%, the mean survival time was12.1months. The patients with strong positive expression of Wnt-1, their6monthssurvival rate was53.3%,12months survival rate was20%,24months survivalrate was0%, the mean survival time was9months, there was statisticalsignificance (x2=8.842,P=0.03).3、β-catenin was all expressed in normal hepatic tissue, non-cancerouscirrhosis hepatic tissue and HCC tissue. β-catenin was mainly displayed in thecell membrane of normal hepatic tissue and non-cancerous cirrhosis hepatictissue, showed by brown continuous linear distribution. There wasn’tsignificant difference between them（Z=-0.240，P=0.877）. The membranousexpression of β-catenin was reduced and discrete, or β-catenin also wasobserved in eytoplasm and/or cellular nueleus in hepatocellular carcinomatissue. The expression of β-catenin was significant different between in normalhepatic tissue and HCC tissue（Z=-3.111，P=0.002）. The expression ofβ-catenin was significant different between in non-cancerous cirrhosis hepatictissue and HCC tissue（Z=-5.590，P=0.000）. The expression of β-cateninwasn’t significant difference in age, sex, HbeAb, HBsAg and the size of tumorin HCC tissue. The adnormal expression of β-catenin was obvious stronger inHCC tissue with the portal vein tumor thrombosis or distant metastasis（Z=-2.588，P=0.010）. The adnormal expression of β-catenin was significantin HCC tissue with≥400ng/ml (Z=-3.678， P=0.000). The adnormalexpression of β-catenin was obvious in HCC tissue with later clinical stage（IIb+IIIa）（x2=16.493,P=0.001）and be with lower pathological classification（x2=23.396,P=0.000）. The patients with normal expression of β-catenin,their6months survival rate was100%,12months survival rate was100%,24months survival rate was30%, The mean survival time was25.9months. Thepatients with adnormal expression of β-catenin, their6months survival ratewas67.6%,12months survival rate was24.3%,24months survival rate was 2.7%, the mean survival time for10.1months. Their prognosis had significantdifference based on single variable Log-rank test（x2=16.387,P=0.000）. Thepatients with normal expression of β-catenin had longger survival time.4、Axin-1protein was expressed strongly and showed by from yellow tobrown scattered or group clumps in normal hepatic tissue, non-cancerouscirrhosis hepatic tissue and HCC tissue. There wasn’t significant difference inthree kinds of tissue. The expression of Axin-1protein wasn’t significantdifference refered to age, sex, HbeAb, HbsAg, size of tumor and the portalvein tumor thrombosis or distant metastasis in HCC tissue. The expression ofAxin-1protein was ierrelevant with The clinical stage of HCC patients (x2=3.930,P=0.269)and ierrelevant with pathological classification (x2=4.630,P=0.099). The expression of Axin-1protein wasn’t relevant with the prognosisof patients(x2=5.615, P=0.06).5、Basing on Cox Regression survival analysis, Only adnormal expressionof β-catenin protein wasn relevant with the prognosis of patients, there wasstatistical significance (P=0.013).6、The exprression of Wnt-1and β-catenin were all highly presented inHCC tissue. The difference of their expression had statistical significance（Z=-3.590,P=0.000）and was positive correlation. Adnormal expression rateof β-catenin was high when the expression of Wnt-1was positive or strongpositive（r=0.513,P=0.000）. The difference of the expression of Wnt-1andAxin-1hadn’t statistical significance（X2=5.768,P=0.123）. The difference ofthe expression of β-catenin and Axin-1hadn’t statistical significance（Z=-0.104,P=0.917）.Conclusions:1、The difference of expression of Wnt-1protein was significant innormal hepatic tissue, non-cancerous cirrhosis hepatic tissue and HCC tissue,the expression of Wnt-1protein in HCC tissue was strongger than that in theother tissue.2、The difference of expression of β-catenin was obvious in normalhepatic tissue, non-cancerous cirrhosis hepatic tissue and HCC tissue, the adnormal expression of β-catenin was obvious stronger in HCC tissue withthe portal vein tumor thrombosis or distant metastasis, AFP≥400ng/ml,later clinical stage and with lower pathological classification, whoseprognosis was worse and had shorter survival time.3、The difference of expression of Axin-1protein wasn’t significant innormal hepatic tissue, non-cancerous cirrhosis hepatic tissue and HCC tissue.4、The expression of wnt-1protein and the adnormal expression ofβ-catenin was positive correlation. The adnormal expressive rate of β-cateninwas higher in HCC tissue with the positive expression or strongly positive.β-catenin was the key protein in the classic wnt signaling pathway, whoseencoding genes will become possiblely new targets in the treatment of livercancer in the future. |
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