We evaluated the clinical usefulness of plasma matrix metalloproteinase-7 (MMP-7) as a diagnostic and prognostic biomarker in patients with renal cell carcinoma (RCC). MMP-7 was quantified in plasma of 50 healthy subjects and 97 RCC patients using a Fluorokine MultiAnalyte Profiling assay. RCC patients were stratified into the following groups: without metastases (N0M0; n = 39), with lymph nodes (N1M0; n = 13), and with distant metastases (M1; n = 45). Diagnostic performance of MMP-7 was analyzed by the receiver operating characteristics (ROC) curve. Kaplan-Meier analysis and the Cox regression model were used to estimate the impact of MMP-7 on the cancer-specific survival outcome of RCC patients. MMP-7 was significantly higher in both metastatic groups N1M0 and M1 (medians, 3.82 and 3.34 µ µ µ µg/L) compared to N0M0 group or controls (medians, 1.85 and 1.64 µ µ µ µg/L; all P < 0.001). In ROC analysis, the area under the ROC curve of MMP-7 was 0.80 in the detection of metastases in RCC (P < 0.0001). In the Kaplan-Meier analysis, patients with MMP-7 above the 95th percentile of controls showed less favorable survival rates compared to those with normal MMP-7 (log-rank test, 15.7; P < 0.0001). High MMP-7 was associated with cancer-related mortality estimated by univariate Cox regression (risk ratio, 4.34, 95% CI, 1.12-10.6; P = 0.032). The multivariate Cox regression model determined MMP-7 (risk ratio, 2.70, 95% CI, 1.39-5.24; P = 0.003) and metastases (risk ratio, 5.81, 95% CI, 2.77-12.2; P < 0.0001) as independent determinants of cancer-related survival outcomes. In conclusion, increased plasma MMP-7 could be related to metastatic disease and poor prognosis in patients with RCC. (1) Due to its asymptomatic clinical course, RCC is being detected incidentally in two-thirds of patients.(2) By the time of diagnosis about 25% of these patients will present with metastatic disease.(3) Frequent sites of metastasis include the lung, bone, liver, and brain.(4) Metastatic spread that often involves more than one organ system significantly impacts upon the survival of RCC patients.(3,5) Therefore, early diagnosis of RCC is a critical issue in the management of these patients. One of the strategies to improve this situation is the identification of biomarkers in plasma or serum samples whose level is sensitive to detect early tumor forms and to monitor for disease progression in RCC. Numerous tumor markers in RCC have been tested in the past, but there are no definitive biomarkers available for such purposes to date.(6) Search in free available mRNA data bases and immunohistochemistry data showed that, among different MMP, matrilysin (MMP-7) is overexpressed in RCC. (7)(8)(9)(10) MMP form a family of zinc-containing enzymes showing the common ability to degrade various components of the extracellular matrix. Both in vitro and in vivo investigations have shown that increased MMP are associated with the invasive and metastatic potential in several malignant tumors such as breast, colorectal, pancreatic, prostate, head/neck re...