PDF(Pubmed)
Abstract：
Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cancer and its pathogenesis is strongly associated with VHL-HIF-VEGF signaling. SHH ligand is the upstream SHH pathway regulator, while GLI1 is its major effector that stimulates as a transcription factor, i.a. expression of VEGFA gene. The aim of present study was to assess the prognostic significance of SHH, GLI1 and VEGFA immunoreactivity in KIRC tissues. The analysis included paired tumor and normal samples from 34 patients with KIRC. The immunoreactivity of SHH, GLI1 and VEGFA proteins was determined by immunohistochemical (IHC) renal tissues staining. The IHC staining results were assessed using the immunoreactive score (IRS) method which takes into account the number of cells showing a positive reaction and the intensity of the reaction. Increased GLI1 protein immunoreactivity was observed in KIRC tissues, especially in early-stage tumors, according to the TNM classification. Elevated expression of the VEGFA protein was noted primarily in high-grade KIRC samples according to the Fuhrman/WHO/ISUP scale. Moreover, a directly proportional correlation was observed between SHH and VEGFA immunoreactivity in TNM 3 + 4 and Fuhrman/ISUP/WHO 3 + 4 tumor tissues as well as in samples of patients with shorter survival. We also observed an association between shorter patient survival as well as increased and decreased immunoreactivity, of the VEGFA and GLI1, respectively. The aforementioned findings suggest that the expression pattern of SHH, GLI1 and VEGFA demonstrates prognostic potential in KIRC.
摘要：
肾透明细胞癌（KIRC）是最常见的肾癌类型，其发病机制与VHL-HIF-VEGF信号密切相关。SHH配体是上游SHH通路调节因子,虽然GLI1是其作为转录因子刺激的主要效应物，i.a.VEGFA基因的表达。本研究的目的是评估SHH的预后意义，KIRC组织中的GLI1和VEGFA免疫反应性。分析包括来自34例KIRC患者的配对肿瘤和正常样品。SHH的免疫反应性，通过免疫组织化学(IHC)肾组织染色确定GLI1和VEGFA蛋白。使用免疫反应性评分(IRS)方法评估IHC染色结果,该方法考虑显示阳性反应的细胞数和反应强度。在KIRC组织中观察到GLI1蛋白免疫反应性增加，尤其是在早期肿瘤中，根据TNM分类。根据Fuhrman/WHO/ISUP量表,在高级KIRC样品中主要注意到VEGFA蛋白的表达升高。此外，在TNM3+4和Fuhrman/ISUP/WHO3+4肿瘤组织以及生存期较短的患者样本中，SHH和VEGFA免疫反应性之间呈正相关。我们还观察到患者生存期较短以及免疫反应性增加和减少之间的关联。分别为VEGFA和GLI1。上述发现表明，SHH的表达模式，GLI1和VEGFA在KIRC中显示出预后潜力。
