Open AccessPlasma matrix metalloproteinase‐7 as a metastatic marker and survival predictor in patients with renal cell carcinomas
Author(s) -
Ramankulov Azizbek,
Lein Michael,
Johannsen Manfred,
Schrader Mark,
Miller Kurt,
Jung Klaus
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00802.x
Subject(s) - medicine , proportional hazards model , renal cell carcinoma , receiver operating characteristic , oncology , gastroenterology , survival analysis , lymph node , univariate analysis , biomarker , confidence interval , percentile , multivariate analysis , pathology , urology , biology , biochemistry , statistics , mathematics
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 µg/L) compared to N0M0 group or controls (medians, 1.85 and 1.64 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. ( Cancer Sci 2008; 99: 1188–1194)