Heterogeneity of Platelet Derived Growth Factor Pathway Gene Expression Profile Defines Three Distinct Subgroups of Renal Cell Carcinomas

血小板衍生的生长因子通路基因表达谱的异质性定义了三种不同的肾细胞癌亚组

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作者:Adela Maria Ferician, Ovidiu Catalin Ferician, Andrei Dragos Cumpanas, Patricia Lorena Berzava, Alexandru Nesiu, Ariana Barmayoun, Anca Maria Cimpean

Aim

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. Materials and

Conclusion

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.

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.

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