Roles of HOTAIR in lung cancer susceptibility and prognosis

Long noncoding (lncRNA) single-nucleotide polymorphisms (SNPs) are associated with the susceptibility to the development of various malignant tumors. The aim of this study was to investigate the roles of HOX transcript antisense intergenic RNA (HOTAIR) and its SNPs in lung cancer.

Initially, the expression of HOTAIR in different tumors was investigated using the online Gene Expression Profiling Interactive Analysis (GEPIA) resource. Three SNPs (rs920778, rs1899663, and rs4759314) of HOTAIR were identified using the MassArray system. Following this, the relationship between these SNPs and susceptibility to lung cancer was investigated.

Expression of HOTAIR was found to increase in a variety of cancers, including nonsmall cell lung cancer (NSCLC). We found that the genotypes of these SNPs (rs920778, rs1899663, and rs4759314) were not significantly associated with lung cancer type, family history, lymph node metastasis, or lung cancer stage. In gender stratification, the results of rs920778 genotypes showed that, compared to genotype AA, the AG (OR = 0.344, 95% CI: 0.133-0.893, p = .028) and AG + GG (OR = 0.378, 95% CI: 0.153-0.932, p = .035) genotypes of rs920778 are protective factors against NSCLC in females. In smoking stratification, compared with AA of rs920778, the genotype AG + GG (OR = 0.507, 95% CI: 0.263-0.975, p = .042) was a protective factor against NSCLC in nonsmoking people. No statistical differences were observed in the classifications of rs1899663 and rs4759314 genotypes. Linkage disequilibrium analysis revealed a high linkage disequilibrium between the rs920778 and rs1899663 (D' = 0.99, r²  = .74), rs920778 and rs4759314 (D' = 0.85, r²  = .13), and rs1899663 and rs4759314 (D' = 0.79, r²  = .00).

Our study demonstrated that HOTAIR expression increased in NSCLC, and that the genotypes of rs920778 could be useful in the diagnosis and prognosis of lung cancer.