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Association Of MicroRNA-related Gene (DROSHA,DICER1 And GEMIN4) Polymorphisms With T-cell Lymphoma Prognosis

Posted on:2018-06-14Degree:MasterType:Thesis
Country:ChinaCandidate:X B TianFull Text:PDF
GTID:2334330518467789Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background:T-cell lymphomas(TCL)are a group of heterogeneous tumors of l ymphoid hematopoietic system which originate from mature or posterior thymus T lymphocytes and natural killer cells.The majority of TCL is more malignant than B cell lymphoma,and the prognosis is poor.The incidence of TCL in our country is significantly higher than that in western countries,accounting for about 25% of lymphoma.Based on the International Prognostic Index(IPI),there have been specific IPIs for different subtypes of lymphomas which are formatted by combining with their own characteristics and other prognostic factors,in order to evaluate the prognosis of patients.However,there is increasing evidence that prove IPI is not so effective for all subtypes of TCL.Micro RNAs(mi RNAs)are a class of endogenous,highly conserved,small noncoding RNA molecules comprised of 21~24 nucleotides,which are involved in regulation of gene transcription.Recently several studies have reported that mi RNAs are associated with the development and progression of cancers.Single nucleotide polymorphisms(SNPs)are the most common forms of genetic variation in the human genome,and the polymorphisms of mi RNA-related genes are related to the synthesis and the downstream biological effects of miRNAs.However,there are few studies about the association of miRNA-associated gene polymorphisms with the prognosis of TCL patients.Objective:This study was aimed to analyze the association of microRNA-related gene DROSHA single nucleotide polymorphisms(SNP)rs10719 and rs6877842,DICER1 rs3742330 and GEMIN4 rs3744741 with prognosis of T-cell lymphoma.Materials and Methods:Using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method,we examined the genotypes of the above 4 SNPs in the peripheral blood samples of 163 TCL patients.Then we analyzed the association of the 4 SNPs with complete remission(CR)rate and overall survival(OS).Results:The association analysis of clinical features with CR rate and OS rate showed that pathological type,tumor stage,serum lactate dehydrogenase level and IPI score were significantly correlated with CR rate and OS rate of TCL patients.Logistic-regression analysis showed that rs6877842 and rs3742330 were independent prognostic factors for CR of TCL patients.Patients carrying the rs6877842 CG genotype had a significantly higher CR rate compared with those carrying the CC genotype(OR = 0.07,95%CI 0.01-0.72,P = 0.026);the same as patients carrying the DICER1 rs3742330 GG genotype compared with those carrying the GA genotype(OR = 0.15,95%CI 0.02-0.97,P = 0.047)or the AA genotype(OR = 0.11,95%CI 0.02-0.71,P = 0.020).Multivariate Cox model analysis showed that rs3742330 was an independent prognostic factor for OS of TCL patients.Patients with the rs3742330 GG genotype had a significantly improved OS compared with those carrying the GA(HR = 9.02,95%CI 1.22-66.92,P = 0.031)or AA genotype(HR = 8.77,95%CI 1.19-64.67,P = 0.033).The other two SNPs of rs10719 and rs3744741 had no significant association with CR or OS.Conclusions:DROSHA rs6877842 and DICER1 rs3742330 are independent prognostic factors for TCL CR and DICER1 rs3742330 is also an independent prognostic factor for TCL OS.
Keywords/Search Tags:MicroRNA, single nucleotide polymorphism, T-cell lymphoma, prognosis
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