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Expression And Significance Of MTOR And EIF4E In HCC Tissues

Posted on:2015-04-01Degree:MasterType:Thesis
Country:ChinaCandidate:L M SongFull Text:PDF
GTID:2284330431493660Subject:General surgery
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BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumours.It has always been a huge threat to human life due to its high malignancy, fast diseaseprogress and high mortality rate. The incident symptoms of HCC are relativelyunnoticeable in early stage patients, but this disease develops very quickly, and whenit is diagnosed most patients are already in the late stage or this disease has distantmetastasis, making the treatment and prognosis very difficult. The main reason to thisphenomenon is this tumour’s high metastasis rate and high recurrence rate. Thenumber of people dying of HCC also ranks third among all the malignant tumours.One of the most obvious characteristics of HCC’s tumorigenesis and progress istumor cell’s excessive division and proliferation. Cell division and proliferationdemand necessary material substance produced via the activation of proteinreplication system to produce large amount of protein. Because of this, large amountof protein synthesis in cell is an absolutely necessary condition to tumor cell divisionand proliferation. In cell division and proliferation,mammalian target of rapamycin(mTOR) plays a critical regulatory role, this point has been demonstrated by somestudy, while the abnormity of eukaryotic initiation factor4e(elF4E), locating in thedownstream of mTOR, is closely related to tumorigenesis and progress. mTOR canbe activated via phosphorylation, which in turn can phosphorylate elF4E’s4E-BP1.Once being phosphorylated,4E-BP1will dissociate from elF4E and free elF4E can activate protein translation initiation, which will synthesize protein and provide thematerial substance for cell mitosis and play a critical role in tumorigenesis andprogress.ObjectiveThe objective of this experiment is to study the expression and significance ofmTOR and elF4E in HCC, and analyse the relevance between the two, exploring theirfunctions in HCC tumorigenesis and progress and their clinical significance, in orderto provide theoretical basis for HCC’s early diagnosis and medical treatment.MethodsData are collected from45HCC patients who have had surgery at ZhengzhouUniversity First Affiliated Hospital from June2012to July2013. Among them, thereare31male patients, aged from29to68, averaged at48.36, and14female patients,aged from32-73, averaged at51.41. All the patients experienced surgery for the firsttime, none of them have undergone any form of radiotherapy and chemotherapy fortumor treatment, and all of them are confirmed with HCC via pathologicalexamination. Streptavidin Peroxdase Conjugated Method are adopted to measure theexpression of mTOR and elF4E in liver cancer tissue, para-carcinoma tissue, anddistal liver tissue. Biosens Digital Imaging System v1.6(Shanghai Bio-Tech Co., Ltd.)is used to carry out quantitative analysis of experimental results image, which usesAverage Density to represent the marker staining intensity of immunoreaction results,after which, statistical method is adopted to analyse the relevance between mTORand elF4E protein, and the relations between their clinical pathologicalcharacteristics.Results1mTOR expression in tissue: mTOR is expressed in liver cancer tissue,para-carcinoma tissue, and distal liver tissue. After comparing each two of these threetissues, expression difference is found and such difference is statistically meaningful, p<0.05; the relation of mTOR expressed in these three tissues is: liver cancer tissue>para-carcinoma tissue> distal liver tissue.2ElF4E expression in tissue: elF4E is expressed in in liver cancer tissue,para-carcinoma tissue, and distal liver tissue. After comparing each two of these threetissues, expression difference is found and such difference is statistically meaningful,p<0.05; the relation of mTOR expressed in these three tissues is: liver cancer tissue>para-carcinoma tissue> distal liver tissue.3Both mTOR and elF4E are expressed in liver cancer tissue, para-carcinomatissue, and distal liver tissue. In liver cancer tissue: rs=0.315, p=0.006; inpara-carcinoma tissue: rs=0.445,p=0.003; in distal liver tissue: rs=0.392,p=0.014. Inthese three sets of data, p<0.05, rs is positive number, which means in all three set,mTOR expression and elF4E expression have correlation, and they are positivelycorrelated.Conclusion:1Expression level of mTOR and elF4E in HCC cancer tissue is significantlyhigher than that in para-carcinoma tissue, while that in para-carcinoma tissue issignificantly higher than that in distal liver tissue. This signifies that mTOR andelF4E, as cancer-related gene, can play biological role in HCC’s tumorigenesis andprogress.2mTOR and elF4E show positive correlation in HCC expression, and havesynergistic effect in cancer cell proliferation and invasion, and both participate inHCC’s invasive growth. Consequently, giving targeting therapy to mTOR and elF4Eat the same time might point out a new direction to research on non-surgery HCCtreatment.
Keywords/Search Tags:Primary liver cancer, mTOR, eIF4E, Hepatic tissueImmunohistochemistry
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