Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9.

Abstract

PURPOSE: In this study, we investigated the association between matrix metalloproteinase (MMP)-9 RNA expression in primary colorectal cancer (CRC) and standard clinicopathologic variables and determined whether levels of MMP-9 RNA predict relapse and survival. PATIENTS AND METHODS: Tumor and paired normal mucosa specimens from 71 primary CRC patients following resections were assessed. RNA levels were determined via Northern blot hybridization and quantitated with laser densitometry. Results were expressed as tumor/normal mucosa (T/N) fold-increase calculated after normalizing for RNA loading using 28S expression. Statistical analysis was performed using the SAS statistical package procedure. Kaplan-Meier survival curves were compared with the two-sided log-rank test. RESULTS: The mean T/N MMP-9 RNA fold-increase was 9.4 +/- 1.0 (mean +/- SE) (P < .001). Overexpression of MMP-9 RNA correlated significantly with status of synchronous distant metastases (M stage) (P = .004) and Dukes' stage (P = .008). A T/N fold-increase of 5.0 was used to discriminate between high (> 5.0) and low (< or = 5.0) T/N MMP-9 expression. High T/N MMP-9 RNA expression was associated with a significantly shorter disease-free (P = .0001) and overall (P = .0002) survival duration. In univariate and multivariate analyses, T/N MMP-9 RNA level was found to be an independent prognostic factor for disease-free survival. CONCLUSION: This report provides the first evidence that increased MMP-9 RNA production in primary human CRC may be a powerful, independent predictor of recurrence and outcome.