Moreover, RCC is associated with an extensive and complex array of genetic defects, further complicating the clinical picture. The homeobox gene PROX1 is an evolutionarily conserved transcription factor that controls cell differentiation and plays essential roles during embryonic development of the lens, retina, liver, pancreas, and lymphatic vasculature. Although the role of PROX1 in embryonic organogenesis and lymphatic vasculogenesis is well established, little is known about its function in adult tissues. In recent studies, both oncogenic and tumorsuppressive functions have been ascribed to PROX1 in a variety of different human cancers. PROX1 participates in the transition from benign colon adenoma to carcinoma, and in mouse hemangioendothelioma cells, stable overexpression of PROX1 induces an invasive phenotype and promotes expression of genes involved in cell migration. On the other hand, PROX1 expression is down-regulated in pancreatic cancer tissues, and loss of PROX1 function is associated with decreased patient survival. In carcinomas of the biliary system, epigenetic silencing and genomic deletions of the PROX1 gene, and the attendant SKF 81297 hydrobromide drastic reduction in PROX1 protein levels, suggest that PROX1 acts as a tumor suppressor. Nevertheless, the exact mechanisms by which PROX1 regulates the differentiation and proliferation of cancer cells to influence overall prognosis are largely unknown. PROX1 is multifunctional protein whose physiological functions may change according to developmental stage, organ, or type of cancer. Previous investigations have documented that PROX1 mRNA is expressed in both human embryonic and adult kidney tissues. A recent cancer gene profiling study revealed that PROX1 mRNA is significantly decreased in renal cancer tissue CGP 36216 hydrochloride compared to adjacent normal tissue. These observations raise the question of whether a relationship exists between PROX1 and RCC, a question that has not yet been studied. Here, we investigated the expression of PROX1 in human RCC and subsequently explored the potential role played by PROX1 in the tumorigenesis and development of RCC. The present study represents the first examination of the tumorigenic and prognostic significance of altered PROX1 protein expression in RCC patients. In our initial studies, we found that both PROX1 mRNA and protein expression were clearly reduced in RCC tissues compared with adjacent normal tissues. Unexpectedly, however, the aberrant expression of PROX1 was positively correlated with advanced disease stages and metastasis, and negatively correlated with patients�� OS.