Decreased Thrombospondin-1 and Bone Morphogenetic Protein-4 Serum Levels as Potential Indices of Advanced Stage Lung Cancer

Abstract

Introduction: Lung cancer belongs to the most common carcinoma worldwide and is the leading cause of cancer-related death. Bone morphogenetic protein-4 (BMP-4) is extracellular signaling molecule involved in many important processes, including cell proliferation and mobility, apoptosis and angiogenesis. Thrombospondin-1 (TSP-1) belongs to the extracellular matrix proteins. It participates in the cell-to-cell and cell-to-matrix interactions and thus plays important role in tumor microenvironment for cancer development and metastasis formation. Aim: To investigate serum levels of TSP-1 and BMP-4 together with BMP-4 polymorphism in lung cancer patients. Material and Methods: A total of 111 patients (76 men) with newly diagnosed lung cancer, including 102 patients with non-small cell lung cancer and 9 patients with small-cell lung cancer. Advanced stage of lung cancer was diagnosed in 99 (89%) of patients: stage IV—in 48, stage IIIB—in 33, stage IIIA—in 18 patients; there were six patients with stage II and six patients with stage I. The control group consisted of 61 healthy persons. In all the subjects, serum levels of BMP-4 and TSP-1 were measured by ELISA. With a Real-Time PCR system genotyping of BMP-4 was performed. Results: BMP-4 and TSP-1 serum levels were significantly lower in the patients with lung cancer than in the controls (TSP-1:10,109.2 ± 9581 ng/mL vs. 11,415.09 ± 9781 ng/mL, p < 0.05; BMP-4: 138.35 ± 62.59 pg/mL vs. 226.68 ± 135.86 pg/mL p < 0.001). In lung cancer patients TSP-1 levels were lower in advanced stages (9282.07 ± 4900.78 ng/mL in the stages III-IV vs. 16,933.60 ± 6299.02 ng/mL in the stages I-II, p < 0.05) and in the patients with than without lymph nodes involvement (10,000.13 ± 9021.41 ng/mL vs. 18,497.75 ± 12,548.25 ng/mL, p = 0.01). There was no correlation between TSP-1 and BMP-4 serum levels. BMP-4 gene polymorphism did not influence the results of the study. Conclusion: Decreased levels of TSP-1 and BMP-4 may serve as potential indices of lung cancer, with additional importance of low TSP-1 level as a marker of advanced stage of the disease.