| Objective(s):Detecting the distribution in blood samples of miRNA-219,Let-7,miRNA-499 gene single nucleotide polymorphisms in patients with cervical cancer,cervical intraepithelial neoplasia and healthy control population,then analysis the correlation between these SNP,providing new ideas for the pathogenesis,treatment and prognosis of cervical cancer.Methods:1.From October 2016 to December 2018,459 cases of cervical cancer,180 cases of cervical intraepithelial neoplasia were treated as experimental group,and 561 outpatient health checkups were used as control group.(For the Han nationality in Yunnan),blood samples were collected.2.Three miRNAs related to PI3K/AKT signaling pathway were screened by mirPath v.3 database,namely miRNA-219,Let-7,miRNA-499,and the SNP related to the signaling pathway was found through 1000 Genome Browser database.At the locus one SNP locus was selected,corresponding to rs 107822,rs 10877887,rs3746444;3.The Taqman probe genotyping method was applied to detect alleles,genotypes of rs107822(miRNA-219),rs10877887(let-7),rs3746444(miRNA-499)in all samples The Spearman correlation coefficient was used to analyze the correlation between case group and control group and SNP locus.The chi-square test was used to calculate the distribution of SNP alleles and genotypes in cervical cancer,cervical intraepithelial neoplasia and healthy subjects.Frequency and difference,multiple logistic regression analysis of miRNA-219,let-7,miRNA-499 gene polymorphism and the development of cervical cancer;4.Collect clinical datas of patients with cervical cancer,including the age of the patient,the number of maternal and childbirth,different pathological types and prognostic factors including the degree of tissue differentiation,clinical stage,depth of myometrial invasion,vascular infiltration of lymph vessels,maximum diameter of tumor Etc.,the distribution and difference of SNP locus in the cervical cancer group were analyzed,and the relationship between these SNPs and the pathogenesis and prognosis of cervical cancer was analyzed.Results:1.Correlation analysis showed that rs 107822(miRNA-219)allele C,T and genotype C/C,C/T,T/T and cervical cancer,cervical intraepithelial neoplasia,the control group was related,The P=0.002,but the correlation was weak.The correlation coefficients were 0.062 and 0.090.The distribution of alleles in the cervical cancer group VS healthy control group and cervical intraepithelial neoplasia group VS control group had statistical differences.The significance of learning(P=0.003 and 0.012),and the frequency of allele C in the cervical cancer group,cervical intraepithelial neoplasia group was significantly higher than the control group,suggesting that rsl07822 allele C may be cervical cancer(OR=1.305;95%CI:1.093-1.559)and risk factors for cervical intraepithelial neoplasia(OR=1.362;95%CI:1.071?1.734).The frequency of genotype C/C,C/T in the cervical cancer group,cervical intraepithelial neoplasia group was significantly higher than that of the control group,while the genotype T/T distribution frequency was significantly lower than the control group,different genotypes There was a statistically significant difference in the frequency of VS control group between the VS control group and the cervical intraepithelial neoplasia group(P=0.011 and 0.020).However,the frequency of distribution of the SNP locus allele,genotype cervical cancer group and cervical intraepithelial neoplasia group was not statistically significant(P=0.774 and 0.556).2.Let-7 gene mutation site rs10877887,miRNA-499 gene mutation site rs3746444 alleles and genotypes in cervical cancer,cervical intraepithelial neoplasia and control group distribution frequency difference is not statistically significant,P>0.05.3.Hierarchical analysis showed that rs107822(miRNA-219),rs 10877887(let-7),rs3746444(miRNA-499)alleles and genotypes and age of onset of cervical cancer patients,initial gestational age and prognostic factors Including FIGO stage,degree of tumor differentiation,depth of local cervical myometrial invasion,lymph node metastasis,and maximum tumor diameter were not significantly correlated,P>0.05.However,the distribution frequency of rs3746444 allele A,G showed a difference in the number of births of cervical cancer patients,P=0.040 and 0.017,and the frequency of allele A was>4 times in pregnancy and>3 times in birth.The patients were significantly elevated in comparison with the number of pregnant women<4 times and the number of times of birth<3 times,indicating that with pregnancy,the increase in parity,allele A in cervical cancer(OR=1.470;95%CI:0.734)?1.271)/(OR=1.760;95%CI:1.104?2.806)is a risk factor.However,there was no significant difference in the distribution frequency of genotypes A/A,A/G,G/G in pregnancy and parity,and the P>0.05.4.There was no significant difference in the distribution of rs107822(miRNA-219)alleles C and T between the LSIL(CIN1)group and the HISL(CINII,CINIII)group,P=0.223.However,the distribution of genotypes C/C,C/T,T/T was statistically significant in the two groups,P=0.008,and the LSIL group genotype C/T was significantly more than the HSIL group,T/T genotype Less than the HSIL groupConclusion(s):1.The alleles C,T and genotypes C/C,C/T,T/T of rs107822(miRNA-219)are associated with susceptibility to cervical cancer in Yunnan Han women,among which allele C may be cervical cancer and Risk factors for cervical intraepithelial neoplasia.Genotypes C/C and C/T may increase the risk of cervical intraepithelial neoplasia and cervical cancer.The difference in the frequency of distribution of genotypes C/C,C/T,and T/T in LSIL and HSIL was statistically significant.The C/T genotype may play a role in the progression of cervical intraepithelial neoplasia from low to high levels.Sexual effects,while the T/T genotype is a risk factor.However,this site may not be significantly associated with the progression of cervical intraepithelial neoplasia to cervical cancer.Rs107822(miRNA-219)may be a target for the prediction of cervical cancer and precancerous lesions,guiding the diagnosis of cervical lesions,and providing a basis for accurate treatment.2.rs 10877887(Let-7)alleles and genotypes may not play a role in the development of cervical cancer and cervical intraepithelial neoplasia.The age,age of first trimester,maternal parity and post-effects of cervical cancer patients included FIGO stage,tumor differentiation,depth of myometrial invasion,lymph node metastasis,and maximum tumor diameter.3.Although rs3746444(miRNA-499)alleles and genotypes may not play a role in the development of cervical cancer and cervical intraepithelial neoplasia.However,in the stratified analysis,the distribution of rs3746444 alleles A and G in different pregnancy and delivery times of cervical cancer patients may be different.Allele A may be cervical cancer in women with gestational times?4 times or?3 times.The risk factor.It further indicates that the occurrence of cervical cancer is related to the susceptibility of the host,and provides a theoretical basis for the mechanism of action of multiple pregnancy and prolificacy as one of the causes of cervical cancer. |
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