Relationships of Coagulation Factor XIII Activity with Cell-Type and Stage of Non-Small Cell Lung Cancer

PURPOSE: Factor XIII (FXIII), a thrombin-activated plasma transglutaminase zymogen, is involved in cancer development and progression through a triggered coagulation pathway. The aim of this study was to examine whether FXIII activity levels differed in non-small cell lung cancer (NSCLC) patients according to histological types and TNM stage when compared with healthy subjects. MATERIALS AND METHODS: Twenty-eight NSCLC patients and 28 normal controls who had been individually age-, gender-, body mass index-, smoking status-, and smoking amount-matched were enrolled: 13 adenocarcinomas, 11 squamous cell carcinomas, and four undifferentiated NSCLCs; four stage I, two stage II, 12 stage III, and 10 stage IV NSCLCs. FXIII activity was measured using fluorescence-based protein arrays. RESULTS: The median FXIII activity level of the NSCLC group [24.2 Loewy U/mL, interquartile range (IQR) 14.9-40.4 Loewy U/mL] was significantly higher than that of the healthy group (17.5 Loewy U/mL, IQR 12.6-26.4 Loewy U/mL) (p=0.01). There were no differences in FXIII activity between adenocarcinoma (median 18.6 Loewy U/mL) and squamous cell carcinoma (median 28.7 Loewy U/mL). NSCLC stage significantly influenced FXIII activity (p=0.02). The FXIII activity of patients with stage III NSCLC (median 27.3 Loewy U/mL, IQR 19.3-40.5 Loewy U/mL) was significantly higher than those of patients with stage I or II (median 14.0 Loewy U/mL, IQR 13.1-23.1 Loewy U/mL, p=0.04). FXIII activity was negatively correlated with aPTT in NSCLC patients (r=-0.38, p=0.04). CONCLUSION: Patients with advanced-stage NSCLC exhibited higher coagulation FXIII activity than healthy controls and early-stage NSCLC patients.

Role of crosslinked protein in lung injury following total body irradiation and bone marrow transplantation

The aberrant protein crosslinks formation during lung injury as results total body irradiation (TBI) and bone marrow transplantation (BMT) therapy has been examined as apossible contributory factor in organ or tissue pathogenesis. Female C3HeB/ FeJ mice were used for an experimental animal. Carbon monoxide uptake (V(CO)) was measured at 1, 2, 3, 4 and 5 months after TBI at respective doses of 12, 14, 16 and 18 Gy 16 h prior to syngeneic BMT. Also as a measure of aberrant protein crosslinking in the inured tissues, transglutaminase (TGase)-activities and crosslinked protein were examined along with thrombin, a protease known to activate TGases. Reductions of VCO were detected following TBI and BMT. Activities of thrombin and TGase 1, and crosslinked protein in bronchoalveolar lavage (BAL) fluid of the mice 1 wk after TBI at 12 Gy and BMT were identified and found to be elevated in the treated animals. These findings suggest that elevated levels of crosslinked proteins and TGase I in the bronchoalveolar larvage during the lung injury could have enhanced the organ pathogenesis following TBI and BMT.