P1.03-025 Serum KL-6 Levels in Patients with Lung Cancer

Abstract

Serum levels of KL-6 are widely used as an indicator of activity of interstitial lung disease. Although KL-6 was initially developed as a serum marker for malignancies, it is still unknown if KL-6 can be used as a biological marker of lung cancer. This study aimed to determine the properties of serum KL-6 levels in patients with lung cancer. First, serum KL-6 elimination kinetics after resection of lung cancer was investigated in 7 patients. Postoperative time course of serum KL-6 levels was analyzed using non-linear least square analysis with the fitting equation; C(t)=C0exp(-kt)+Cp, where k is the rate constant of elimination. The biological half-life was calculated as loge2/k. Next, serum KL-6, CEA, and CYFRA levels of patients with lung cancer and benign chest disease were retrospectively reviewed. A total of 226 patients with lung cancer and 103 patients with benign chest disease were included in this study. Serum KL-6 levels were measured using the electrochemiluminescence immunoassay method. The cut-off level of KL-6 was 500 U/ml. Rate constant of elimination and biological half-life of KL-6 in initial 7 patients were 0.827±0.275 day-1 and 0.93±0.35 day, respectively. These data implies that lung cancer cells produce KL-6 molecule and release it into the serum. Among 329 patients, serum KL-6 levels were above the cut-off level in 44 patients (19.5%) with lung cancer and 4 patients (3.9%) with benign chest disease. The mean serum KL-6 level in patients with lung cancer was significantly (p=0.0027) higher (375 ± 232 U/ ml) than that in patients with benign chest disease (296 ± 177 U/ml). Serum KL-6 levels in patients with lung cancer were significantly correlated with tumor size (p<0.0001), stage (p<0.0001), and individual TNM descriptors (T; p<0.0001, N; p=0.0047, M; p=0.0003). ROC analysis revealed that AUC of KL-6 was 0.6348 (p=0.0015), and that was inferior to CEA (AUC=0.8127, p<0.0001) and CYFRA (AUC=0.7103, p<0.0001). The sensitivity, specificity, true positive rate, true negative rate, and accuracy of KL-6 were 19.5%, 95.0%, 91.7%, 35.2%, and 43.5%, respectively. Serum KL-6 levels are well correlated with the progressiveness of lung cancer. KL-6 might be useful as a biological marker to monitor the recurrence and the effect of therapy in lung cancer.