Usefulness of bone resorption markers CTX, TRAP5b, and PINP in patients with non-small cell lung cancer and bone metestases. Preliminary report study

Background: Non-small cell lung carcinoma (NSCLC) is the most common lung cancer, which represents the major cause of cancer death worldwide. The early diagnosis of NSCLC is difficult, and the sensitivity of common serum tumor markers, such as carcinoembryonic antigen (CEA) and fragments of cytokeratin 19 (CYFRA 21-1), is low. Unfortunately, bone metastases (BMs) are common in patients with NSCLC, and their early detection and treatment may improve both disease-free interval and survival. Several serum biomarkers have been proposed for the detection of BMs, such as 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), which are markers of bone resorption. The aim of this preliminary study was to evaluate the usefulness of a panel of serum biomarkers in patients with NSCLC and BMs. Patients and methods: Sixteen patients (11 males, 5 females, median age 64 years, range 54-68) with NSCLC and BMs (cases), and 18 age- and gender-matched patients without BMs (controls) underwent serum CTX, TRAP5b, PINP, CEA, and CYFRA 21-1 measurements. CTX was measured by automated immunometric assay, TRAP5b and CEA by two-site enzyme-linked immunosorbent assay (ELISA), PINP by radioimmuno assay (RIA), and CYFRA 21-1 by immunochemiluminescent assay. The cut-off values were 400 pg/mL (CTX), 5 U/L (TRAP5b), 3.5 ng/mL (CEA), 65 μg/L (PINP), and 45 pg/mL (CYFRA 21-1), respectively. Results: CTX (443.7±945.1 vs. 402.7±28.4 pg/mL, p=0.003), and PINP (75.9±11.4 vs. 64.1±7.5 μg/L, p=0.001), were significantly higher in patients with BMs, while the other markers did not differ (p=NS) between cases and controls. The sensitivity, specificity and accuracy were 73.7%, 86.7%, and 79.4% (OR=18.2, 95% CI 2.99-110.7, p<0.0001) for CTX; 30.4%, 76.2%, and 67.6% (OR=6.22, 95% CI 1.06-36.5, p=0.038) for TRAP5b; 72.2%, 81.2%, and 76.5% (OR=11.26, 95% CI 2.21-57.20, p=0.002) for PINP; 55.5%, 62.5%, and 58.8% (OR=2.08, 95% CI 0.53-8.23, p=0.29) for CEA; 65.0%, 78.61%, and 70.6% (OR=6.81, 95% CI 1.41-32.8, p=0.012) for CYFRA 21-1, respectively. Conclusions: In patients with NSCLC, both CTX and PINP measurements can be useful in the detection of BMs.