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Association Between Hsa-miR-196a2 Functional Polymorphism And Prognosis After Platinum-Based Chemotherapy Of Advanced Non-Small Cell Lung Cancer Patients In A Chinese Population

Posted on:2011-08-13Degree:MasterType:Thesis
Country:ChinaCandidate:X Y ZhanFull Text:PDF
GTID:2154360308960015Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Non-small-cell lung cancer(NSCLC)takes approximately 85% of the incidence of lung cancer worldwide. Its prognosis keeps poor and mortality remains high. Moreover, the amount of NSCLC patients in China is increasing rapidly.The variations of DNA sequence,for instance, single nucleotide polymorphism (SNP),are the results of influence from external interference factors to organism. These variations could be stably transmitted to future generations and some of them are related to diseases.MicroRNAs (miRNAs),an abundant class of endogenous small noncoding RNAs,function as negative regulators by causing posttranscriptional gene silencing, and participate in multitudinous biological process.Recent studies revealed it that mutations or ectopic expression of miRNAs were associated with various kinds of cancer.It might play the roles of both cancer suppressor gene and proto-oncogene.SNPs in miRNAs could alter miRNA expression and maturation, and change the property of miRNA afterwards. Thus,plentiful target genes and maturation process of pre-miRNA would be affected, and lead to totally different results of biochemical and physiological process.Rs11614913, an SNP in mature sequences of hsa-miR-196a2, was reported that its variant homozygote CC had associations with significantly increased risk of several cancer and poor NSCLC survival in Chinese population.This paper is aimed to investigate the associations between hsa-miR-196a2 rs11614913 and response and severe toxicity after platinum-based regimen in advanced NSCLC patients.We successfully screened this polymorphism in 442 Chinese patients,and individuals of homozygous CC obtained significantly higher occurrence of grade 3 or 4 toxicity. Our results indicated that CC genotype was an unfavorable factor for NSCLC prognosis, and it was similar to the result of Hu et al.'s previous research.The current status of NSCLC prognosis is far from satisfactory, suggesting finding biomarkers for individualized therapy, which could acquire best curative effect,lest side effects, and finally improve quality of life and extend survival.Hsa-miR-196a2 rs11614913 is highly possible to become such a biomarker in the future.
Keywords/Search Tags:non-small-cell lung cancer, platinum-based chemotherapy, prognosis, hsa-miR-196a2, SNP
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