Abstract
Urothelial cell carcinoma (UCC) is the commonest malignant tumor of the urinary tract and the second most common kidney cancer malignancy. Growth arrest-specific 5 (GAS5), a long noncoding RNA, is encoded by the GAS5 gene and plays a critical role in cellular growth arrest and apoptosis. In the current study, two single nucleotide polymorphisms (SNPs) in the GAS5 gene, rs145204276 and rs55829688, were selected to investigate correlations between these single SNPs and susceptibility to UCC. A total of 430 UCC cases and 860 ethnically matched healthy controls were included. SNP rs145204276 and SNP rs55829688 were determined using a TaqMan genotyping assay. Logistic regression models demonstrated that female patients with UCC carrying the rs145204276 GAS5 Ins/Del or Del/Del genotype had a 3.037-fold higher risk of larger tumor status (95% confidence interval 1.259–7.324) than did rs145204276 wild type (Ins/Ins) carriers (p = 0.011). The Cancer Genome Atlas validation cohort analysis demonstrated that the expression of GAS5 in female patients with bladder urothelial carcinoma (BLCA) with larger tumor size was much lower than that in patients with a smaller tumor size (p = 0.041). Kaplan-Meier curve analysis and the log–rank test revealed that female patients with BLCA and lower GAS5 expression had poorer overall survival than those with higher GAS5 expression. In conclusion, genetic variations in GAS5 rs145204276 may serve as a critical predictor of the clinical status of female patients with UCC.
Highlights
Urothelial cell carcinoma (UCC), called transitional cell carcinoma, typically involves the urinary system and can develop in the lining of epithelial cells of the urethra, ureters, renal pelvis, or Diagnostics 2020, 10, 260; doi:10.3390/diagnostics10050260 www.mdpi.com/journal/diagnosticsDiagnostics 2020, 10, 260 bladder [1]
Whether Growth arrest-specific 5 (GAS5) single nucleotide polymorphisms (SNPs) affect susceptibility to UCC remains unclear. In this case-control study, we identified the relationship between two GAS5 polymorphisms and clinical characteristics in Taiwanese patients with UCC
195 patients (45.3%) had muscle-invasive urothelial carcinomas, 340 (79.1%) had a higher stage of tumor progression (T1–T4), and 51 (11.9%) and 14% (3.3%) of patients had lymph node metastasis (N1 + N2) and cancer spread to other parts (M1), respectively
Summary
Urothelial cell carcinoma (UCC), called transitional cell carcinoma, typically involves the urinary system and can develop in the lining of epithelial cells of the urethra, ureters, renal pelvis, or Diagnostics 2020, 10, 260; doi:10.3390/diagnostics10050260 www.mdpi.com/journal/diagnosticsDiagnostics 2020, 10, 260 bladder [1]. UCC is the predominant histologic type in the United States, accounting for more than. 90% of all bladder cancers; approximately 25% of patients with bladder cancer have muscle-invasive disease [2]. UCC of the bladder represents the fifth most commonly diagnosed malignancy in the United States [3], and patients with bladder cancer usually present with painless hematuria. Clinical delays in the diagnosis of bladder cancers are frequent, because the symptoms are similar to those of various benign diseases, such as urinary tract infection, kidney stones, and prostatic hyperplasia. For patients with high-grade malignancy of UCC, systemic chemotherapy is the standard treatment, providing a median survival of 15 months. Immunotherapy offers a new hope to patients with UCC that progresses after their initial systemic therapy [4]. The armamentarium for the treatment of advanced or metastatic UCC is expanding
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