Weng Wei-Chun, Chen Chih-Jung, Chen Pei-Ni, Wang Shian-Shiang, Hsieh Ming-Ju, Yang Shun-Fa
Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435, Taiwan.
Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 356, Taiwan.
Diagnostics (Basel). 2020 Apr 28;10(5):260. doi: 10.3390/diagnostics10050260.
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 ( = 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 ( = 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.
尿路上皮癌（UCC）是最常见的泌尿系统恶性肿瘤，也是第二常见的肾癌恶性肿瘤。生长停滞特异性5（GAS5）是一种长链非编码RNA，由GAS5基因编码，在细胞生长停滞和凋亡中起关键作用。在本研究中，选择了GAS5基因中的两个单核苷酸多态性（SNP），即rs145204276和rs55829688，来研究这些单SNP与UCC易感性之间的相关性。总共纳入了430例UCC病例和860名种族匹配的健康对照。使用TaqMan基因分型检测法确定SNP rs145204276和SNP rs55829688。逻辑回归模型表明，携带rs145204276 GAS5 Ins/Del或Del/Del基因型的UCC女性患者出现较大肿瘤状态的风险比rs145204276野生型（Ins/Ins）携带者高3.037倍（95%置信区间1.259 - 7.324）（P = 0.011）。癌症基因组图谱验证队列分析表明，肿瘤较大的膀胱尿路上皮癌（BLCA）女性患者中GAS5的表达远低于肿瘤较小的患者（P = 0.041）。Kaplan-Meier曲线分析和对数秩检验显示，GAS5表达较低的BLCA女性患者的总生存期比GAS5表达较高的患者差。总之，GAS5 rs145204276的基因变异可能是UCC女性患者临床状态的关键预测指标。
