Department of Medical Biology, Faculty of Medicine, Ordu University, 52200, Altınordu, Ordu, Turkey.
Ulubey Vocational Higher School, Ordu University, 52850, Ulubey, Ordu, Turkey.
Mol Biol Rep. 2019 Oct;46(5):5287-5294. doi: 10.1007/s11033-019-04985-3. Epub 2019 Jul 24.
Truncated KIT (tr-KIT) is an alternative variant of c-KIT protein. Previous studies have clearly documented that c-KIT was associated with various oncogenic processes in RCC. However, the biological significance of tr-KIT in RCC development and progression remains unclear. So, it was aimed to investigate the possible association between RCC and tr-KIT which is thought to activate some oncogenic pathways. In this study, Kidney Cancer cDNA Array containing a total of 48 cDNA samples from the normal kidney tissues of 9 healthy subjects and kidney tumor tissues of 10 stage-1, 5 stage-2, 13 stage-3 and 11 stage-4 RCC patients was used for gene expression analysis. Real-Time PCR method was used to measure tr-KIT/c-KIT expression ratios. tr-KIT/c-KIT expression ratio was compared between tumor and normal samples, and statistically correlated with the clinical parameters of RCC patients. tr-KIT/c-KIT expression ratio was approximately 4-times higher in tumor samples than control ones (p = 0.001). Also, tr-KIT/c-KIT expression ratio was approximately two, three and six times higher in Fuhrman nuclear grades 2, 3 and 4 than normal, respectively (p = 0.009). Moreover, clear cell and papillary RCC has a significantly higher level of tr-KIT/c-KIT expression ratio than chromophobe RCC (p = 0.016). In the current study, it was stated for the first time that tr-KIT/c-KIT expression ratio was up-regulated in RCC tissues, and high tr-KIT/c-KIT expression ratio was correlated with more aggressive clinical features and poor patient prognosis. Our results suggest that increased tr-KIT/c-KIT expression ratio might be useful as a prognostic marker for RCC patients.
截断的 KIT(tr-KIT)是 c-KIT 蛋白的一种替代变体。先前的研究清楚地记录了 c-KIT 与 RCC 中的各种致癌过程有关。然而,tr-KIT 在 RCC 发展和进展中的生物学意义尚不清楚。因此,本研究旨在研究 RCC 与 tr-KIT 之间可能的关联,因为 tr-KIT 被认为可以激活一些致癌途径。在这项研究中,使用了包含来自 9 名健康受试者的正常肾脏组织和 10 名 I 期、5 名 II 期、13 名 III 期和 11 名 IV 期 RCC 患者的肾脏肿瘤组织的总共 48 个 cDNA 样本的肾癌 cDNA 阵列进行基因表达分析。实时 PCR 方法用于测量 tr-KIT/c-KIT 表达比率。比较肿瘤和正常样本之间的 tr-KIT/c-KIT 表达比率,并与 RCC 患者的临床参数进行统计学相关分析。肿瘤样本中的 tr-KIT/c-KIT 表达比率比对照样本高约 4 倍(p=0.001)。此外,tr-KIT/c-KIT 表达比率在 Fuhrman 核分级 2、3 和 4 中分别比正常组织高约 2、3 和 6 倍(p=0.009)。此外,透明细胞和乳头状 RCC 的 tr-KIT/c-KIT 表达比率明显高于嫌色细胞 RCC(p=0.016)。在本研究中,首次表明 tr-KIT/c-KIT 表达比率在 RCC 组织中上调,高 tr-KIT/c-KIT 表达比率与更具侵袭性的临床特征和患者预后不良相关。我们的结果表明,增加的 tr-KIT/c-KIT 表达比率可能可作为 RCC 患者的预后标志物。