IMBALANCE BETWEEN CATHEPSIN-B AND CYSTEINE PROTEINASE-INHIBITORS IS OF PROGNOSTIC-SIGNIFICANCE IN HUMAN LUNG-CANCER

Abstract

In the study of 69 matched pairs of lung tumors and normal lung parenchyma, the median activities of cathepsin B (CB) and cystein proteinase inhibitors (CPI's) in tumors were found to be increased 4.4-fold and twofold, respectively. The levels of CB and CPI activities did not correlate with TNM stages nor with cell differentiation. In addition, CB activity did not vary across the histologies of lung cancer, while CPI activity was significantly higher in squamous cell carcinoma compared to the other cell types (p<0.01). Although the majority of tumor samples had increased CPI activity levels compared to the controls, we could clearly demonstrate an imbalance between the activities of CB and CPIs by determining the ratio of both values. In normal lung parenchyma, the median ratio was 0.59 indicating that CB activity is controlled by excess inhibitors, while in tumor tissue the median ratio was 1.78 suggesting deficiency of inhibitors. There was a significant correlation between CB and CPI activities in normal tissue (r=0.65, p<0.001). No such relationship was observed in the total of tumor tissue. In squamous cell carcinoma (n=30), however, an inverse relationship between the activities of CB and CPIs was observed (r=0.45, p<0.01). Both, CB activity and the ratio of the activities of CB: tumor-control/CPI: tumor-control, were found to be related to survival probability, since increased values were significantly associated with poorer prognosis. It is concluded, that the imbalance between the activities of CB and CPIs is of prognostic significance in lung tumor patients.