GONADOTROPIN BETA-SUBUNIT NICKING ENZYME (GBNE), A POTENTIAL MARKER OF EARLY MALIGNANCIES

GBNE is an arginine-specific metalloprotease that cleaves human chorio nic gonadotropin free beta-subunit in pregnancy serum. We tested GBNE activity in 539 serum samples, from individuals that were healthy, wit h benign diseases, or with a broad mixture of cancers. The mean GBNE a ctivity in 130 samples from healthy individuals, 151 from those with b enign disease, and 258 from cancer patients was 5.4 +/- 0.32, 5.8 +/- 0.20 and 16 +/- 1.2 units, respectively. ROC analysis indicated 86% di scrimination between control samples and cancer. A cut-off of 12 units was selected. This was equaled or exceeded by 3.1% of samples from he althy individuals, 3.9% from those with benign disease, and 57% from t hose with cancer. There was no significant difference in detection of the different cancer primaries, breast (sensitivity 56%), gastrointest inal (53%), genitourinary (62%), gynecological (58%) and lung (55%) ca ncers. Sensitivity was highest for early stage, and lowest for advance d malignancies, for all cancer primaries. Taken together, sensitivity was 70, 44, 43 and 24%, for stages I, II, III and IV respectively. GBN E is suggested to be a nonorgan site-restricted tumor marker with high sensitivity for early stage cancers.