目的:研究的目的是验证假设:转化生长因子TGFβ1-3,其受体TGFβI-III,和细胞内信使蛋白Smad1-7参与肾癌的发病机制?TGFβ/Smads通路的基因在肾细胞癌(RCC)组织中的表达,肿瘤周围组织(TME;肿瘤微环境),和正常的肾脏(NK)组织?。
方法:将20例肾癌患者行全肾切除术纳入分子分析。通过RT-qPCR定量基因的mRNA表达。
结果:研究表明,TGFβ/Smads通路基因在RCC和TME中的表达均失调:与NK组织相比,TME中TGFβ1,TGFβ3表达增加;TGFβ2,TGFβ3,TGFβRI,TGFβRIII,与TME组织相比,RCC中Smad1、Smad2、Smad3和Smad6的表达不足;TGFβRI,TGFβRIII,与NK组织相比,Smad2在RCC中表达不足。
结论:一方面,TGFβ信号通路基因在恶性肿瘤中的低表达可能导致该细胞因子的抗增殖和促凋亡活性丧失.另一方面,TME中TGFβ/Smads途径基因的过表达比肿瘤或NK组织中的过表达最有可能导致肿瘤周围空间中的免疫抑制作用,并且可能对TME中存在的非肿瘤细胞具有抗增殖和促凋亡作用。该区域的功能和形态一致性可以决定肿瘤的侵袭性和肿瘤过程扩散的时间。
OBJECTIVE: The aim of the study was to verify hypotheses: Are transforming growth factors TGFβ1-3, their receptors TGFβI-III, and intracellular messenger proteins Smad1-7 involved in the pathogenesis of kidney cancer? What is the expression of genes of the TGFβ/Smads pathway in renal cell carcinoma (RCC) tissues, peritumoral tissues (TME; tumor microenvironment), and in normal kidney (NK) tissue?.
METHODS: Twenty patients with RCC who underwent total nephrectomy were included into the molecular analysis. The mRNA expression of the genes was quantified by RT-qPCR.
RESULTS: The study showed that the expression of the genes of TGFβ/Smads pathway is dysregulated in both RCC and the TME: TGFβ1, TGFβ3 expression is increased in the TME in comparison to the NK tissues; TGFβ2, TGFβ3, TGFβRI, TGFβRIII, Smad1, Smad2, Smad3, and Smad6 are underexpressed in RCC comparing to the TME tissues; TGFβRI, TGFβRIII, and Smad2 are underexpressed in RCC in comparison to the NK tissues.
CONCLUSIONS: On the one hand, the underexpression of the TGFβ signaling pathway genes within the malignant tumor may result in the loss of the antiproliferative and pro-apoptotic activity of this cytokine. On the other hand, the overexpression of the TGFβ/Smads pathway genes in the TME than in tumor or NK tissues most probably results in an immunosuppressive effect in the space surrounding the tumor and may have an antiproliferative and pro-apoptotic effect on non-neoplastic cells present in the TME. The functional and morphological consistency of this area may determine the aggressiveness of the tumor and the time in which the neoplastic process will spread.