Association Between Polymorphisms In MiRNAS And Primary Lung Cancer

ObjectiveThe aim of this study was to explore the relationship between lung cancer and gene expressions and single nucleotide polymorphisms of plasma miR-126,miR-25,miR-145,and miR-197.Subjects and methods1.Subjects:A total of 148 patients with primary lung cancer were recruited as lung cancer group,and 148 health individuals were selected as the control group.The epidemiological data and peripheral blood samples were collected from each participant.2.Methods:The SYBR Green-based qPCR method was used to detect the expressions of plasma miRNAs.After the peripheral blood leukocyte DNA was extracted,the SNPs of miR-126(rs2297537,rs2297538,rs4636297),miR-25(rs1527423),miR-145(rs41291957,rs4705342,rs353291),and miR-197(rs1889470)were examined using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry.3.Statistical analysis:Statistical analyses were performed using SPSS 21.0.The t test or Mann-Whitney U was used to analyze quantitative data.?~2 test was performed in qualitative data analyze.Logistic regression was used to determine the influencing factors of lung cancer.The significance level?was set at 0.05.Results1.The expression of plasma miRNAs and lung cancerThe miR-126 expression levels of the lung cancer group and the control group were 1.64(0.71,2.83)and 0.77(0.32,1.58),respectively.The expression levels of miR-25 were 1.36(0.77,3.27)and 0.80(0.34,1.73),respectively.The expression levels of miR-145 were 1.11(0.56,2.93)and 0.70(0.44,1.07),respectively.The expression levels of miR-197 were 1.13(0.59,2.29)and 0.59(0.41,1.25),respectively.The difference all had statistical significance(P<0.05).There were significant correlations between the high expression of plasma miR-126 and lymph node metastasis(P<0.05).2.miRNAs SNPs and lung cancer susceptibilityThe gene polymorphisms of miR-145 rs353291 was associated with lung cancer susceptibility;significantly miR-145 rs353291 GG genotype was associated with increased risk of lung cancer compared to AG+AA genotypes(P=0.013).There were statistically significant differences between the metastasis group and metastasis negative group in the distribution of genotypes miR-145 rs41291957(P=0.021)and rs4705342(P=0.026).The risk of metastasis in rs41291957 AA genotype carriers was 3.086 times higher than that of GG genotype carriers(95%CI=1.165~8.170);the risk of metastasis in rs4705342 CC genotype carriers was significantly higher than that in TT genotype carriers(OR=5.829,95%CI=1.383~24.572).The genotypes distribution of miR-126 rs2297537(P=0.004)and rs4636297(P=0.019)were association with tumor stage.The risk of advanced lung cancer in rs2297537 CC genotype carriers was significantly higher than those in CG/GG genotype carriers(OR=3.284,95%CI=1.425~7.569);the risk of advanced lung cancer in rs4636297 AG/AA genotype carriers was significantly higher than that in GG genotype carriers(OR=4.154,95%CI=1.168~14.774).There were statistically significant differences between the lymphatic metastasic group and negative lymphatic metastasic group in the distribution of genotypes miR-126 rs4636297,the risk of lymphatic metastasic in miR-126 rs4636297 AG/AA genotype carriers was7.308 times higher than that of GG genotype carriers(P=0.030).3.Analysis of lung cancer susceptibilityLogistic regression revealed that the risk factors of lung cancer mainly included higher expression of miR-145(OR=1.423,95%CI=1.126~1.798),and miR-145rs353291 GG genotype(OR=1.797,95%CI=1.046~3.087).ConclusionsThe miR-145 high expression and miR-145 rs353291 GG genotype are the risk factors of lung cancer.