MiRNAs are deregulated in metastatic primary ccRCC and could be promising prognostic markers for an early prediction of metastasis. Alterations in miRNA expression characterize distant metastases of different metastatic sites. Furthermore, our study suggests a functional role of miR-30c in metastasis. The miRNAs could be a helpful tool for individual follow-up prediction and personalized therapy selection.

Muscle-invasive bladder cancer (MIBC) represents a highly aggressive tumor type compared to non-muscle-invasive tumors. MIBC is characterized by specific molecular alterations, which may also modulate extracellular tumorigenic effects. Tumor-associated exosomes, especially exosomal miRNAs, are important regulators in the interaction between tumor cells and tumor microenvironment by affecting tumor-promoting processes in target cells. It is important to analyze whether their exosomal patterns also reflect the specific molecular characteristics of MIBC. The aim of this study was to compare the miRNA expression in secreted exosomes from urinary bladder cancer cells (UBC) with different degrees of invasiveness. By electron microscopy, nanotracking analysis and western blot we proofed a high quality of isolated exosomes. Microarray analysis identified an invasion-associated signature of 15 miRNAs, which is significantly altered in exosomes of invasive UBC compared to non-invasive counterparts. Therefrom, 9 miRNAs are consistent differently expressed in both, invasive cells and their secreted exosomes. The remaining 6 exosome-specific miRNAs are only deregulated in exosomes but not in their parental cells. MiRNA alterations were verified by qPCR in cell culture and urinary exosomes. In conclusion, we showed that exosomes from invasive UBC cells are characterized by a specific miRNA signature. Further analyses have to clarify the functional relevance of exosomal miRNAs secreted by invasive bladder cancer cells for modification of the tumor microenvironment and their putative role as molecular markers in liquid biopsies.

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myeloid-derived suppressor cells (MDSC) could be affected by chemotherapy and correlate with pathologic response in bladder cancer patients receiving neo-adjuvant chemotherapy.METHODS: Pretreatment Peripheral blood levels of granulocytic (G-MDSC) and monocytic MDSC (M-MDSC) were measured by fow cytometry. We divided patients into high and low (above and below the median, respectively) groups based on the median value for each immune cell subset and compared outcomes of the two groups.RESULTS: A signi?cant pathological response (pT0-1) was attained in 14% (3 of 22) of patients with low G-MDSC compared with 60% (13 of 22) of patients with high G-MDSC (P¼0.042). Patients with high G-MDSC had signi?cantly shorter diseaseespecific survival and progression-free survival (both P<0.001). In the multivariate analysis for survival, only high G-MSDC levels for progression-free survival (P¼0.022), high G-MDSC and pathological response emerged as independent prognostic factor for diseasespecific survival(P¼0.004 and 0.040 respectively).CONCLUSIONS: These results provide evidence that pretreatment peripheral G-MDSCs can inform the outcome of patients treated with platinum-based neoadjuvant chemotherapy