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Study Of The Correlation Of LIF Gene Polymorphism And Susceptibility Of Hepatocellular Carcinomaand Expression Of LIF In Hepatocellular Carcinoma

Posted on:2020-02-01Degree:MasterType:Thesis
Country:ChinaCandidate:Y F DuFull Text:PDF
GTID:2404330575962645Subject:Clinical Laboratory Science
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?Background and Objective? Hepatocellular carcinoma(HCC)is a common malignant solid tumor in the world,characterized by rapid progression and metastasis,high recurrence rate and poor prognosis.The pathogenesis of HCC is very complex,and has not yet been fully elucidated up to now.Single nucleotide polymorphism(SNP)refers to the nucleic acid sequence polymorphism caused by the change of single nucleotide at the genome level.SNP has been widely used in association analysis because of its high distribution frequency and strong genetic stability.Association analysis of high-frequency SNPs and common diseases is important,improving people's understanding of the pathogenesis of diseases.Early diagnosis and treatment of HCC is of great significance.At present,the most common methods for the diagnosis of HCC are imaging examination and detection of serum tumor markers.Although the above two methods have been widely used in clinical practice,however,imagingexaminations depend on the operator's experience and ability,and the sensitivity and specificity of the used tumor markers are not satisfactory.Therefore,it is still an urgent need to find new methods for early detection of HCC.Leukemia inhibitory factor(LIF),a member of IL-6 cytokine family,is a multifunctional glycoprotein.It has been proved that LIF can inhibit the differentiation of embryonic stem cells,induce protein production in acute response phase of liver cells,stimulate the proliferation of bone marrow cells,induce neurotransmitter conversion of neurons,and inhibit lipoprotein lipase activity of adipocytes.LIF gene expresses constitutively in a variety of cancer cells and plays different roles in different types of tumors.The aim of this study was to investigate the effects of LIF on HCC at gene and RNA levels and to evaluate the possibility of serum LIF as a marker of HCC.?Methods? In this study,we 1)detected the genotypes of two SNP loci(rs929271,rs929273)of LIF gene in patients with liver diseases and healthy people using high-throughout sequence,and evaluated the correlation between genotypes,allele frequencies and haplotypes and susceptibility to HCC;2)determined the expression of LIF and Leukemia inhibitory factor receptor(LIFR)gene in HCC and adjacent liver tissues by qRT-PCR,and analyzed their possible effects on HCC;3)detected the levels of serum LIF protein in four groups,in order to evaluate the clinical significance of LIF in the diagnosis and treatment of HCC.?Results? The results showed that 1)there was no significant correlation between the genotype,dominant model,invisible model and haplotype of the two SNP loci and the susceptibility to HCC,either compared with the healthy control group or the cirrhosis group;2)there was no difference in the expression of LIF in HCC and adjacent liver tissues,and the expression level of LIFR inliver tumor nodules was significantly lower than that in adjacent liver tissues;3)LIF level was the highest in chronic hepatitis B group and the lowest in healthy control group.Compared with the healthy control group,the LIF level in HCC group did not increase significantly.?Conclusion?1.LIF polymorphism was not associated with susceptibility of HCC.2.LIF does not play an important role in promoting the development of HCC;LIFR may have a protective effect on hepatocytes,and the low level of LIFR may be a potential factor in the occurrence of HCC.3.LIF may not be a potential tumor marker of HCC.LIF may be an important cytokine mediating hepatitis.
Keywords/Search Tags:hepatocellular carcinoma, LIF, LIFR, SNP, hepatitis
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