Introduction: Metastatic renal cell carcinoma (RCC) remains the leading cause of mortality in patients with clear cell RCC. While deleted in liver cancer (DLC-1) is known to be closely associated with tumor growth and metastasis in several kinds of human tumors, the function of DLC-1 in clear cell RCC is unclear. Materials and Methods: We quantified DLC-1 mRNA expression in paired tumor and non-tumor samples from 62 patients in clear cell RCC using a real-time reverse transcription polymerase chain reaction (RT-PCR), and DLC-1 protein using Western blotting and immunohistochemistry. The association between DLC-1 and matrix metalloproteinase-2 were analyzed. Results: A high level of DLC-1 mRNA and protein expression in approximately 90% of normal renal specimens, the expression levels of DLC-1 in the primary tumors with synchronous metastases were lower than in those without metastases (p < 0.01). Furthermore, DLC-1 expression inversely correlated with advanced histological grade and stage (p < 0.05). Moreover, it is likely that down-regulated DLC-1 increases matrix invasion abilities of RCC via enhancing matrix metalloproteinase-2 expression. Conclusion: Together, it seems that reduced DLC-1 is involved in tumor expansion phenomena associated with tumor progression, invasion and distant metastasis of RCC.

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