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Active MMP‐2 effectively identifies the presence of colorectal cancer
Author(s) -
Murnane Mary Jo,
Cai Jinguo,
Shuja Sania,
McAneny David,
Klepeis Veronica,
Willett John B.
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24682
Subject(s) - colorectal cancer , zymography , gelatinase , matrix metalloproteinase , medicine , cancer , malignancy , oncology , pathology , gastroenterology
Fully active MMP‐2 is expressed at such low levels in human tissues that studies often fail to confirm its value as a cancer marker despite strong associations with malignancy. Our study utilized careful extraction, accurate activity measurements, standardization to purified controls and a new statistical metric to determine whether active MMP‐2 is an effective indicator of colorectal cancer compared to pro‐MMP‐2 or pro‐MMP‐9. MMP‐2 and MMP‐9 activities were analyzed in matched normal and cancer samples from 269 patients by gelatin zymography, computer‐assisted image analysis, serial dilutions of strong samples and standardization to controls. An index of effect size was designed for comparative evaluation of active MMP‐2, pro‐MMP‐2 and pro‐MMP‐9 activities. For each gelatinase, mean activity and protein levels/mg soluble protein in normal mucosa and colorectal cancer were calculated for the first time with respect to commercial standards. Active MMP‐2 activity, detected in 99% of colorectal cancers, was higher in 95% of cancers (on average 10‐fold) than in normal mucosa. Levels of pro‐MMP‐2 and pro‐MMP‐9, but not active MMP‐9, activities were also significantly higher in cancers versus normal. However, active MMP‐2 activity provided the most effective test for the presence of cancer ( p < 0.0.0001) with an effect size statistically significantly larger than for either pro‐MMP‐2 or pro‐MMP‐9. Receiver operating characteristic (ROC) curves demonstrated that a cut‐off for active MMP‐2 of >44 SDU activity/mg soluble protein (>180 pg/mg), which is three times mean normal levels, would permit detection of colorectal cancer with an estimated sensitivity of 84% and estimated specificity of 93%. © 2009 UICC