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

2019 ◽  
Vol 8 (3) ◽  
pp. 282 ◽  
Author(s):  
Min-Che Tung ◽  
Yu-Ching Wen ◽  
Shian-Shiang Wang ◽  
Yung-Wei Lin ◽  
Jyh-Ming Chow ◽  
...  

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.

Author(s):  
Ming-Dow Tsay ◽  
Ming-Ju Hsieh ◽  
Chia-Yi Lee ◽  
Shian-Shiang Wang ◽  
Chuan-Shu Chen ◽  
...  

Fibroblast growth factor receptor 4 (FGFR4) plays a prominent role in cell proliferation and cancer progression. This study explored the effect of FGFR4 single-nucleotide polymorphisms (SNPs) on the clinicopathological characteristics of urothelial cell carcinoma (UCC). This study was conducted to survey the possible correlation of the polymorphism of FGFR4 to the risk and clinicopathologic characteristics of UCC. Four loci of FGFR4 (rs2011077 T > C, rs351855 G > A, rs7708357 G>A, and rs1966265 A > G) were genotyped via the TaqMan allelic discrimination approach in 428 UCC cases and 856 controls. The results indicated that UCC subjects who carried the SNP rs2011077 TC+CC genotypes were significantly related to a higher tumor stage (odds ratio (OR): 1.751, 95% confidence interval (CI): 1.078–2.846), primary tumor size (OR: 1.637, 95% CI: 1.006–2.662), and histopathologic grading (OR: 1.919, 95% CI: 1.049–3.511). Moreover, the SNP rs1966265 AG+GG genotypes were prominently related to a higher tumor stage (OR: 1.769, 95% CI: 1.082–2.891), primary tumor size (OR: 1.654, 95% CI: 1.011–2.706), and histopathologic grading (OR: 2.006, 95% CI: 1.096–3.674) compared to individuals with AA homozygotes. In conclusion, our data reveal association of FGFR4 polymorphisms with UCC clinicopathologic characteristics. FGFR4 polymorphisms may serve as a marker or therapeutic target in UCC development.


Tumor Biology ◽  
2014 ◽  
Vol 35 (8) ◽  
pp. 7483-7490 ◽  
Author(s):  
Shian-Shiang Wang ◽  
Ming-Ju Hsieh ◽  
Yen-Chuan Ou ◽  
Chuan-Shu Chen ◽  
Jian-Ri Li ◽  
...  

2019 ◽  
Vol 37 (9) ◽  
pp. 573.e9-573.e17 ◽  
Author(s):  
Sheng-Chun Hung ◽  
Shian-Shiang Wang ◽  
Jian-Ri Li ◽  
Chuan-Shu Chen ◽  
Chia-Yen Lin ◽  
...  

Author(s):  
Chien-Chang Li ◽  
Ming-Ju Hsieh ◽  
Shian-Shiang Wang ◽  
Sheng-Chun Hung ◽  
Chia-Yen Lin ◽  
...  

Urothelial cell carcinoma (UCC) is one of the lethal causes of cancer mortality of the genitourinary tract. Carcinogenic epidemiological risk factors exposure and age over 65 years old are associated with UCC risk. Matrix metalloproteinase 11 (MMP11) was suggested as a tumor marker of metastasis and predictor of poor survival in urothelial carcinomas. In this study, we focused on the associations of MMP11 single-nucleotide polymorphisms (SNPs) to UCC susceptibility, clinicopathological characteristics, and prognosis. In this study, real-time polymerase chain reaction was used to analyze five SNPs of MMP11 rs738791, rs2267029, rs738792, rs28382575, and rs131451 in 431 patients with UCC and 650 cancer-free controls. The MMP11 rs28382575 polymorphic “CT” genotype were susceptible to UCC (AOR = 2.045, 95% CI = 1.088 − 3.843; p = 0.026). For MMP11 rs131451, a significant association was found in 166 UCC patients among age ≤ 65 years old who carried MMP11 rs131451 polymorphic “CC” genotype, which is associated with lower risk to develop later tumor T status (T1-T4) (OR = 0.375, 95% CI = 0.159 − 0.887; p = 0.026) compared with the (CT + TT) genotype. Furthermore, patients of UCC with rs738792 polymorphic “CC” genotype were observed to have higher free of relapse (FS) (p = 0.035), disease specific survival rate (p = 0.037), and overall survival rate (p = 0.009) compared with the rs738792 (CT + CC) genotype. In conclusion, our results demonstrated that the MMP11 SNPs are associated with UCC susceptibility, clinical status, and disease survival. The MMP11 polymorphisms may have potential to predict UCC susceptibility and prognosis.


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