Carboxy-terminal Telopeptide (CTX) and Amino-terminal Propeptide (PINP) of Type I Collagen as Markers of Bone Metastases in Patients with Non-small Cell Lung Cancer

The early diagnosis of non-small cell lung carcinoma (NSCLC) is difficult, and 30-40% of patients with NSCLC develop bone metastases (BMs) during the course of their disease. Because the delayed demonstration of skeletal involvement may seriously affect survival, there is a need for early diagnosis of BMs. Unfortunately, the sensitivity of common serum tumor markers is low and they are used mainly for monitoring the efficacy of therapy and detection of recurrence. The aim of this study was to evaluate the utility of a panel of serum biomarkers in patients with NSCLC and BMs. Sixteen patients (11 males, 5 females; median age=64 years, range 54-68 years) with NSCLC and BMs (cases), and 18 age- and stage-matched patients without BMs (controls) underwent measurement of serum carboxy-terminal telopeptide of type I collagen (CTX), tartrate-resistant acid phosphatase isoform type 5b (TRAP5b) and amino-terminal propeptide of type I collagen (PINP), carcinoembryonic antigen (CEA) and fragments of cytokeratin 19 (CYFRA 21-1. CTX (443.7 +/- 1945.1 vs. 402.7 +/- 28.4 pg/ml, p=0.003) and PINP (75.9 +/- 11.4 vs. 64.1 +/- 7.5 mu g/l, p=0.001) were significantly higher in patients with BMs, while the mean value of the other markers did not differ (p=NS) between cases and controls. The sensitivity, specificity and accuracy were 73.3%, 86.7% and 79.4% for CTX; CEA; 65.0%, 78.6% and 70.6% for CYFRA; 30.4%, 76.2% and 67.6% for TRAP5b; and 72.2%, 81.2% and 76.5% for PINP, respectively. The area under the receiver operating characteristic curve (AUC) for CTX was 0.68. In conclusion, CTX and PINP measurement can be useful in monitoring patients with NSCLC during follow-up, with the aim of detecting BMs early.55.5%, 62.5% and 58.8% for