Expression Of ERK1/2 Caveolin In Hepatocellular Carcinoma And The Relationship Between ERK1/2 And Caveolin

Background and Objective:It is well known that primary hepatocellular carcinoma(HCC)is a common malignant tumor[1].Among primary liver cancers,hepatocellular carcinoma(HCC)accounts for 85-90%of all cases[30].Hepatocellular carcinoma(HCC)is still a major health problem,which often diagnosed at an advanced stage.Therefore,it’s very important for reachers to investigate thoroughly the occurrence,multiplication and invasivemechanismof hepatocellular carcinoma(HCC).Several signalling pathways are implicated in tumour development and progression,epidermal growth factor receptor(EGFR)signaling pathway,mitogen-activated protein kinase(MAPK)pathway and IKB/NF-κB signaling pathway.Among these pathways,the Ras/MAPKpathway is activated in 50-100%of human HCCs.Hepatoma cells recognize and respond to extracellular stimuli by engaging specific intracellular programs,such as the signaling cascade that leads to activation of the mitogen-activated protein kinases(MAPKs).As an effector molecule on the MAPK signaling pathway,ERKparticipates in a series of physiological processes,such as cell growth,multiplication,differentiation.The abnormal expression of ERK plays an important role in the malignant transformation of cells and proliferation,differentiation and invasion of tumors[4].In addition,recent studies have found that lipid rafts on cell membranes also play a critical role in the occurrence,proliferation and differentiation of liver cancer.As an significant component of lipid rafts,Caveolin is particularly abundant in endothelial cells,where it regulates various functions,including transcytosis,permeability,vasculartone and angiogenesis.Joo[76]has reported thatcaveolin is a major component of caveolae and has been recently identified as an oncogene.Caveolin expression is downregulated in some sortof cancer,including mesenchymal tumors and sarcomas[73].On the contrary,in other cancer types;for example,prostatic carcinoma,Caveolinexpression is high[76].These findings suggest that Caveolinhas multiple actions in human cancercells.The aim of the present study was to investigatethe expression and significance of ERK,Caveolinnus,KI-67in hepatocellular carcinoma(HCC).Then,we would like to study the relationship between ERK,Caveolin and the occurrence,development and invasiveness of HCC.Simultaneously,the other objective is to explore the relationship between erk and caveolin.lt may provide evidence for a theoretical basis for the clinical treatment of.liver cancer,the abatement of invasion and metastasis of liver cancer and the invention and application of new targeted drugs.Methods:1.Tissue samples,including HCC,paracancerous liver tissue(<lcm from liver cancer tissue and>lcm from liver cancer tissue),were all obtained from 121 patients with HCC who had consecutively under-gone surgical resections between ctober 2015 to October 2016 in Zhongshan Hospital affiliated to Xiamen University.2.All the 121 patients were diagnosed and histopathologically confirmed with HCC.The patients’ clinical records and histopathologic diagnoses were fully reviewed.3.According to the experimental requirements,the corresponding tumor tissues,the corresponding non-tumor tissues were obtained from the same 121 patients:one piece of liver cancer tissue,one piece of normal liver tissue adjacent to carcinoma(<1cm from liver cancer tissue),and one piece of normal liver tissue around distant cancer tissue(>1cm from liver cancer tissue).The tissue size of each block was about 1.8×1.8×0.3cmm.Then paraffin sections were made,and the expression of ERK,Caveolinine,KI-67 was detected by immunohistochemical method in the tumor tissues,adjacent liver tissues and distal paracancerous liver tissues.4.The tissue slides were observed under microscope,and the immunohistochemical results were correctly interpreted,recorded,sorted out,and the experimental data were analyzed and summarized by statistical method and analysis software.5.To summarize the expression and significance of ERK,Caveolin in hepatocellular carcinoma(HCC)and the relationship between ERK,Caveolin and KI-67.6.Discuss the impact of ERK,caveolin on tumor development,invasion and the specific molecular mechanism.Simultaneously,explore the relationship between erk and caveolin.Results:It was found that:1.The expression of ERK1/2 in HCC tissues was significantly higher than that in paracancerous tissues in terms of expression intensity and frequency,and the difference was statistically significant(P<0.05).However,there was no significant difference in the expression of ERK1/2 between the adjacent normal liver tissues and the distal adjacent normal liver tissues(P>0.05).2.The expression of Caveolin in HCC tissues was significantly higher than that in paracancerous tissues(P<0.05).There was no significant difference in the expression of Caveolin between the adjacent normal liver tissues and the distal adjacent normal liver tissues(P>0.05).3.By chi-square test,we found that the expression of ERK 1/2 in HCC tissues was correlated with the size,invasiveness of HCC and the index of KI-67(p<0.05),while the expression of ERK 1/2 in HCC tissues was uncorrelated with the age and sex of the patients.Other clinical factors,such as tumor differentiation,were not significantly related.4.The expression of caveolin in HCC tissues was correlated with the size,invasiveness of HCC and the index of KI-67(p<0.05),while the expression of ERK1/2 in HCC tissues was uncorrelated with the age and sex of the patients.Other clinical factors,such as tumor differentiation,were not significantly related.5.By chi-square test,it was found that the ERK1/2 was correlated with Caveolin statistically.Conclusions:1.The expression of ERK1/2 in HCC tissues was significantly higher than that in paracancerous tissues in terms of expression intensity and frequency,and the difference was statistically significant(P<0.05).However,there was no significant difference in the expression between the adjacent liver tissues and the distal adjacent liver tissues,and the difference was not statistically significant(p>0.05).2.The expression of ERK1/2 in HCC was correlated with the size,invasiveness and KI-67 index of HCC(p<0.05).The expression of ERK1/2 in HCC was not related to the age,sex and differentiation of HCC.3.The expression of Caveolin in HCC tissues was significantly higher than that in paracancerous tissues(P<0.05).However,there was no significant difference in the expression between the adjacent liver tissues and the distal adjacent liver tissues,and the difference was not statistically significant(p>0.05).4.The expression of Caveolin in HCC was correlated with the size,invasiveness and KI-67 index of HCC(p<0.05).The expression of erkl/2 in HCC was not related to the age,sex and differentiation of HCC.Hypothesis:Since both ERK and Caveolin are related to the size,invasiveness and KI-67 index of hepatocellular carcinoma.In addition,there is a correlation between ERK and Caveolin.So we can propose a new hypothesis that the invasion and metastasis of hepatoma cells is the result of interaction between ERK and caveolin.This will provide a theoretical basis for the clinical treatment of liver cancer,the abatement of its invasiveness and the invention and application of new targeted therapeutic drugs.