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

BACKGROUND/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 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. 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.

Urinary Microbiota-Are We Ready for Prime Time? A Literature Review of Study Methods' Critical Steps in Avoiding Contamination and Minimizing Biased Results.

Within the last few years, there have been an increased number of clinical studies involving urinary microbiota. Low-biomass microbiome sequencing (e.g., urine, lung, placenta, blood) is easily biased by contamination or cross-contamination. So far, a few critical steps, from sampling urine to processing and analyzing, have been described (e.g., urine collection modality, sample volume size, snap freezing, negative controls usage, laboratory risks for contamination assessment, contamination of negative results reporting, exploration and discussion of the impact of contamination for the final results, etc.) We performed a literature search (Pubmed, Scopus and Embase) and reviewed the published articles related to urinary microbiome, evaluating how the aforementioned critical steps to obtain unbiased, reliable results have been taken or have been reported. We identified different urinary microbiome evaluation protocols, with non-homogenous reporting systems, which can make gathering results into consistent data for similar topics difficult and further burden the already so complex emerging field of urinary microbiome. We concluded that to ease the progress in this field, a joint approach from researchers, authors and publishers would be necessary in order to create mandatory reporting systems which would allow to recognize pitfalls and avoid compromising a promising field of research.