Pretreatment serum syndecan-1 levels and outcome in small cell lung cancer patients treated with platinum-based chemotherapy

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2003-08, Vol.41 (2), p.171-177
• Main Authors: Anttonen, Anu, Leppä, Sirpa, Ruotsalainen, Tarja, Alfthan, Henrik, Mattson, Karin, Joensuu, Heikki
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carboplatin; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Chemotherapy; Cisplatin; Female; Humans; Lung cancer; Lung Neoplasms - blood; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Male; Medical sciences; Membrane Glycoproteins - blood; Middle Aged; Pharmacology. Drug treatments; Pneumology; Prognosis; Proteoglycans - blood; Randomized Controlled Trials as Topic; Survival Analysis; Syndecan; Syndecan-1; Syndecans; Treatment Outcome; Tumors of the respiratory system and mediastinum
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/S0169-5002(03)00196-X

Syndecan-1 is a multifunctional transmembrane heparan sulphate proteoglycan (HSPG) that is present on a variety of cell types. The extracellular syndecan domains can be shed from the cell surface in a highly regulated process called ectodomain shedding. We studied the influence of soluble syndecan-1 on outcome in 88 small cell lung cancer (SCLC) patients treated within the context of two randomised clinical trials with platinum-based therapy. Serum syndecan-1 concentrations were determined using enzyme-linked immunosorbent assay (ELISA) from sera taken prior to initiation of chemotherapy. Patients with the serum syndecan-1 level within the highest tertile (>212 μg/l) had only 38% 1-year and 3% 2-year survival, whereas 58% of those with a lower serum level survived for 1 year and 25% for 2 years following the diagnosis ( P=0.0034). A high serum syndecan-1 level (>212 μg/l) was associated with a high pretreatment lactate dehydrogenase (LDH) level ( P=0.0024) and a poor Karnofsky's performance status ( P=0.021), but not with the clinical stage or the presence of distant metastases at diagnosis. A high serum syndecan-1 level had independent influence on survival also in a multivariate analysis (the relative risk, RR, 1.68; 95% CI, 1.02–2.77; P=0.044) together with the clinical stage (RR, 1.72; 95% CI, 1.05–2.82; P=0.032). We conclude that high pretreatment serum syndecan-1 level is associated with poor prognosis in SCLC treated with platinum-based chemotherapy.