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

Abstract

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 HOX transcript antisense RNA (HOTAIR) was shown to promote tumor progression and be associated with a poor prognosis in multiple cancers including bladder cancer. Polymorphisms of HOTAIR were recently linked to a predisposition for diverse malignancies. Herein we conducted a case-control study to evaluate whether genetic polymorphisms of HOTAIR were associated with UCC risk and clinicopathologic characteristics. Four loci (rs920778 T>C, rs1899663 G>T, rs4759314 A>G, and rs12427129, C>T) of HOTAIR 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): 1.01–3.64, p = 0.047) and a lower overall survival rate (p = 0.008). Moreover, patients with a smoking habit or younger age (≤65 years), who had at least one T allele of HOTAIR rs12427129 were at a higher risk of developing advance tumor T satge (p = 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: 0.28–0.94, p = 0.031). Further analyses of clinical datasets revealed correlations of the expression of HOTAIR with tumor metastasis and a poor survival rate in patients with UCC. Our results verified the diverse impacts of HOTAIR variants on UCC susceptibility and clinicopathologic characteristics.

Involvement of FGFR4 Gene Variants on the Clinicopathological Severity in Urothelial Cell Carcinoma

“…For instance, the genome expression may be enhanced due to the activation of a promoter, according to previous research [26]. In a clinical aspect, the SNPs can result in the various influences on diseases development including cancers [12,[27][28][29][30]. In previous studies, SNPs play an important role in the progression and prognosis of UCC via multiple pathways including WNT1-inducible signaling pathway protein 1-, HOX transcript antisense RNA-, and high mobility group box 1 gene-related routes [6,12,31].…”

“…The SNPs referred to two distinct nucleotide alleles existing in a significant proportion of the whole human population [14]; these are the most plentiful resource of genetic variations and can locate at the exons, introns, and promoters, as well as 50-and 30-untranslated regions [12,25]. The locus and the sequence of SNPs will influence the effect of such polymorphism on transcription and translation [12]. For instance, the genome expression may be enhanced due to the activation of a promoter, according to previous research [26].…”

“…In a clinical aspect, the SNPs can result in the various influences on diseases development including cancers [12,[27][28][29][30]. In previous studies, SNPs play an important role in the progression and prognosis of UCC via multiple pathways including WNT1-inducible signaling pathway protein 1-, HOX transcript antisense RNA-, and high mobility group box 1 gene-related routes [6,12,31]. Concerning FGFR, which plays an important role in both the neoplasm transformation and skeletal growth [32], the different expression of FGFR family and the following tumor microenvironment are the main mechanisms of cancer development [33], in which the FGFR inhibitor has been assessed as a therapeutic option for cancer [34,35].…”

“…The DNA extraction used a method practiced in the literature [12]. Genomic DNA was extracted from the buffy coat fraction of the blood samples by using the QIAamp DNA blood mini kit (Qiagen, Valencia, CA, USA) according to the manufacturer's instructions.…”

“…Single-nucleotide polymorphisms (SNPs) have been established in preceding research to have an important role in cancer progression and prognosis [11][12][13]. Located in various regions of DNA, SNPs can alter the production of transcript factors and following translation and gene expression.…”