目的:我们先前描述了四种不同的血管模式(网状,弥漫,束状,和小梁)在肾细胞癌(RCC)中,提示血管周围细胞的早期和异质性获取很可能是由于特定的PDGF途径基因表达谱。本研究的目的是研究PDGF通路基因表达谱,分别为每个血管模式。
方法:对先前通过组织病理学评估的12例ccRCC进行了PDGF途径的TaqMan测定,免疫组织化学,和RNAscope。基因表达谱与分级相关,入侵,血管模式,和VEGF。
结果:PIK3C3和SLC9A3基因在所有血管模式中均过表达,但在网状和弥漫性模式中,它们与高VEGFmRNA显著相关。STAT1,JAK2,SHC2,SRF和CHUK(IKK)在弥漫性血管型病例中完全过表达。SLC9A3、CHUK和STAT3在G2肿瘤中过表达。
结论:定义了三个ccRCC亚组:1)PIK3C3(VSP34)/SLC9A3,可能适合抗PIK3C3抑制剂;2)VEGFhigh亚组,其中抗VEGF的关联可能是有益的;3)JAK2/STAT1亚组,可能有资格接受与IKK抑制剂相关的抗JAK/STAT治疗。
OBJECTIVE: We previously described four different vascular patterns (reticular, diffuse, fasciculate, and trabecular) in renal cell carcinoma (RCC) suggesting an early and heterogeneous acquisition of perivascular cells most probably due to a particular PDGF pathway gene expression profile. The aim of the study was to study PDGF pathway gene expression profiles, separately for each vascular pattern.
METHODS: TaqMan assay for the PDGF pathway was performed on twelve cases of ccRCC previously evaluated by histopathology, immunohistochemistry, and RNAscope. Gene expression profile was correlated with grade, invasion, vascular patterns, and VEGF.
RESULTS: PIK3C3 and SLC9A3 genes were overexpressed in all vascular patterns, but they were significantly correlated with high VEGF mRNA in the reticular and diffuse pattern. STAT1, JAK2, SHC2, SRF and CHUK (IKK) were exclusively overexpressed in cases with diffuse vascular pattern. SLC9A3, CHUK and STAT3 were overexpressed in G2 tumors.
CONCLUSIONS: Three ccRCC subgroups were defined: 1) PIK3C3 (VSP34)/SLC9A3 which may be proper for anti PIK3C3 inhibitors; 2) VEGFhigh subgroup where association of anti VEGF may be a benefit and 3) JAK2/STAT1 subgroup, potentially being eligible for anti JAK/STAT therapy associated with IKK inhibitors.