Roles Of The Long Non-coding RNA HOTAIR In Lung Cancer Susceptibility And Prognosis

Objective:This study exploring the method was used to explore the association between HOTAIR single nucleotide polymorphisms and lung cancer susceptibility with case-control study method,which is helpful to discover new susceptibility genes and provide new tumor markers for screening and diagnosis of lung cancer.Then,the public database was used to explore the expression and prognosis of HOTAIR in lung adenocarcinoma and lung squamous cell carcinoma,and provide a scientific basis for the prognosis of lung cancer.Methods:The study subjects were from two hospitals in Shandong Province.The sample size included 196 cases and 196 controls.Through the gene database NCBI,the specific sequence of the HOTAIR locus was found,and three loci rs920778,rs 1899663 and rs4759314 were identified.Mass spectrometry are applied to determine genotyping.Using the software SPSS 24.0,statistical analysis of case and control data was performed using two independent sample t-tests,chi-square test,and Kruskal Wallis H test,and logistic regression model was taken to study the odds ratio of each genotype in the case group to the control group and the odds ratio after adjusting each factor.SHEsis software was accustomed to perform linkage disequilibrium and haplotype analysis of each gene locus.In addition,using the websites GEPIA and UALCAN to explore the total expression level of HOTAIR,HOTAIR expression in different genders and different races in patients with lung adenocarcinoma and lung squamous cell carcinoma,Kaplan-Meier model analysis of lung adenocarcinoma and lung squamous cell carcinoma patients in different genders,The relationship between different ethnic expressions and prognosis.Results:This study analyzed the relationship between polymorphisms in three loci and lung cancer susceptibility.The distribution of genotypes AA,AG,GG and AG+GG at rs920778 was 62.0%,32.6%,5.4%and 38.0%,and the distribution in the control group was 56.8%,37.7%,5.5%and 43.2%.The distribution of genotypes AA,AC,CC and AC+CC at rs1899663 was 2.1%,27.5%,70.4%and 97.9%,and the distribution in the control group was 2.7%,31.9%,65.4%and 97.3%.The distribution of genotypes AA and AG of rs4759314 locus was 90.3%and 9.7%in the case group,and 91.3%and 8.7%in the control group.Therefore,it was suggested that there was no significant association between polymorphisms in the three loci and lung cancer susceptibility.The lung cancer patient locus rs 1899663 genotype was different in lung cancer type grouping,P=0.008.In addition,stratified analysis showed that genotype AG(OR=0.344,95CI%:0.133-0,893,P=0.028)and AG+GG(OR=0.378,95%CI:0.153-0.932,P=0.035)can be considered as a protective factor for lung cancer compared with genotype AA in rs920778 locus of the female classification;the rs920778 locus in the non-smoking classification,the genotype AG+GG(OR=0.507,95%CI:0.263-0.975,P=0.042)was also different from the genotype AA,having a key role to inhibit the development of lung cancer.But,the loci rs920778 and rs4759314 genotypes were not statistically different in the case group.In addition,the linkage disequilibrium analysis of HOTAIR polymorphism and lung cancer susceptibility showed that there was a high degree of linkage disequilibrium between rs920778 and rsl899663(D’=0.99,r2=0.74),rs920778 and rs4759314(D’=0.85,r2=0.13).The HOTAIR gene had a higher expression level in both lung adenocarcinoma and lung squamous cell carcinoma than normal samples.The expression level of HOTAIR gene in male and female patients with lung adenocarcinoma or lung squamous cell carcinoma was higher than that of normal samples,and the results were all P<0.001.Among lung adenocarcinoma patients,the HOTAIR expression in Caucasian,African American and Asian patients were different from those in normal samples.The results were P<0.001,P=0.015,P=0.018.In patients with lung squamous cell carcinoma,the levels of HOTAIR expression in Caucasians and Asians also differ from those in normal samples,whose results were separately P<0.001,P=0.024.There was a difference between Caucasians and Asians,P=0.001 in HOTAIR expression of patients.In addition,in patients with lung adenocarcinoma and lung squamous cell carcinoma,there was no significant difference in survival analysis between the HOTAIR gene high expression group and the low expression group,and there had the same effect in gender and ethnicity.Conclusions:The results of this study showed no significant correlation between HOTAIR single nucleotide polymorphisms and lung cancer susceptibility.The rs1899663 locus genotype was significantly different in lung cancer type grouping.The risk of rs920778 locus is related to gender and type of smoking.Patients with lung adenocarcinoma and lung squamous cell carcinoma have high expression of HOTAIR gene in different genders and ethnicities,but it is not yet indicated that HOTAIR is a prognostic factor for lung cancer.