Our findings suggest that specific miRNAs are involved in metastasis and have an impact on the progression of the ccRCC. Furthermore, we identified specific miRNAs characterising very aggressive tumours with early metastasis. In addition, we determined candidate markers associated with survival of the patients. Thus, it seems possible to use miRNAs for prediction of progression to distant metastasis and prognosis analysing the primary tumour.
Currently used clinicopathological parameters are insufficient for a reliable prediction of metastatic risk and disease-free survival (DFS) of patients with clear-cell renal cell carcinoma (ccRCC). To identify prognostic genes, the expression profiles of primary ccRCC obtained from patients with different DFS -eight synchronously, nine metachronously and seven not metastasized tumors -were determined by genome-wide expression analyses. Synchronously and metachronously metastasized primary ccRCC differed in the expression of 167 genes. Thirty-six of these genes were also differentially expressed in synchronously vs. metachronously developed pulmonary metastases analyzed in a previous study. Because of their DFS-associated deregulation that is concordant in metastases and primary ccRCC, these genes are potentially functionally involved in metastatic tumor growth and are also prognostically useful. A prognostic impact was confirmed for the genes CD31, EDNRB and TSPAN7 at the mRNA level (n 5 86), and for TSPAN7 at the protein level (n 5 106). Patients with a higher gene expression of EDNRB or TSPAN7, or with TSPAN7-positive vessels in both cores investigated on tissue microarrays had a significantly longer DFS and tumor-specific survival (TSS). Patients with a higher CD31 gene expression showed a significantly longer TSS. EDNRB was an independent prognostic marker for the DFS. CD31, EDNRB and TSPAN7 had an independent impact on the TSS. In summary, comparative analysis of primary tumors and metastases is appropriate to identify independent prognostic markers in ccRCC. Gene expression of CD31 and EDNRB, and endothelial TSPAN7 protein level are potentially useful to improve outcome prediction because of their independent prognostic impact.The development of macroscopic metastases is the major cause of tumor-associated deaths. 1,2 Clear-cell renal cell carcinoma (ccRCC), which is the most frequent type of kidney cancer, 3 causes initial or metachronous metastases in about 50% of the patients. 4 The median five-year survival rate of patients with metastatic ccRCC accounts for only 11-20%. 5 The disease-free survival (DFS) until manifest metastases develop differs extremely in these patients and results in a very diverse disease outcome. The DFS reflects the dormancy period that tumor cells can undergo after they have settled in a secondary organ. This latency can persist for many years. 2 It is supposed to be caused by suppressed tumor cell proliferation, inhibited angiogenesis or antitumor immune responses. 6 Currently used clinicopathological parameters are insufficient for a reliable outcome prediction for ccRCC patients. The molecular prognostic markers known to date are not suitable for a routine clinical use. 7 Therefore, new molecular markers are urgently needed to predict individual metastatic risk and DFS of ccRCC patients. Such markers represent the
Data suggest that specific chromosomal alterations in clear cell renal cell carcinoma can be used to predict metastasis and cancer specific survival in patients with clear cell renal cell carcinoma. It seems possible to design a combined fluorescence in situ hybridization assay based on these genetic targets for outcome prediction, which can be used for routine diagnostics.
We determined a metastatic signature of clear cell renal cell carcinoma by microarray analysis. Our data provide the possibility of defining the metastatic potential of primary clear cell renal cell carcinoma based on a select number of genes even in a localized situation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.