Impact of Long Non-Coding RNA <i>HOTAIR</i> Genetic Variants on the Susceptibility and Clinicopathologic Characteristics of Patients with Urothelial Cell Carcinoma

• Main Authors: Min-Che Tung, Yu-Ching Wen, Shian-Shiang Wang, Yung-Wei Lin, Jyh-Ming Chow, Shun-Fa Yang, Ming-Hsien Chien
• Format: Article
• Language: English
• Published: MDPI AG 2019-02-01
• Series: Journal of Clinical Medicine
• Subjects: long non-coding RNA; HOX antisense intergenic RNA; polymorphism; susceptibility; clinicopathologic characteristics; urothelial cell carcinoma
• Online Access: https://www.mdpi.com/2077-0383/8/3/282

Increasing evidence shows that dysregulated expression of long non-coding (lnc)RNAs can serve as diagnostic or prognostic markers in urothelial cell carcinoma (UCC), the most common pathological type of bladder cancer. lncRNA <i>HOX transcript antisense RNA</i> (<i>HOTAIR</i>) was shown to promote tumor progression and be associated with a poor prognosis in multiple cancers including bladder cancer. Polymorphisms of <i>HOTAIR</i> were recently linked to a predisposition for diverse malignancies. Herein we conducted a case-control study to evaluate whether genetic polymorphisms of <i>HOTAIR</i> were associated with UCC risk and clinicopathologic characteristics. Four loci (rs920778 T&gt;C, rs1899663 G&gt;T, rs4759314 A&gt;G, and rs12427129, C&gt;T) of <i>HOTAIR</i> were genotyped by a TaqMan allelic discrimination method in 431 cases and 862 controls. We found that female patients who carried AG + GG genotype of rs4759314 were associated with an increased UCC risk after controlling for age and tobacco consumption (adjusted odds ratio (AOR) = 1.92, 95% confidence interval (CI): 1.01&#8315;3.64, <i>p</i> = 0.047) and a lower overall survival rate (<i>p</i> = 0.008). Moreover, patients with a smoking habit or younger age (&#8804;65 years), who had at least one T allele of <i>HOTAIR</i> rs12427129 were at a higher risk of developing advance tumor T satge (<i>p</i> = 0.046), compared to those patients with CC homozygotes. In contrast, rs920778 C allele carriers were negatively correlated with the development of lymph node metastasis (OR = 0.51, 95% CI: 0.28&#8315;0.94, <i>p</i> = 0.031). Further analyses of clinical datasets revealed correlations of the expression of <i>HOTAIR</i> with tumor metastasis and a poor survival rate in patients with UCC. Our results verified the diverse impacts of <i>HOTAIR</i> variants on UCC susceptibility and clinicopathologic characteristics.