Clinical significance of serum soluble death receptor 5 concentration in locally advanced non-small cell lung cancer patients

There is an urgent requirement for the identification of suitable biomarkers for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). The present study aimed to measure the levels of serum soluble death receptor 5 (sDR5) in patients with locally advanced stage III NSCLC, and to evaluate its diagnostic and prognostic significance in these patients. The sDR5 concentrations were evaluated by the enzyme-linked immunosorbent assay method in 50 healthy controls and 122 patients with locally advanced stage III NSCLC [including 57 adenocarcinoma (ADC) and 65 squamous cell carcinoma (SCC) patients], before and after concurrent chemoradiotherapy. It was found that the pretreatment sDR5 levels in patients with NSCLC were higher than the sDR5 levels of healthy controls (P<0.001). However, no significant difference in the sDR5 levels was observed between the ADC and SCC subgroups (P=0.874). According to multiple clinical classifications, a significant increase in the pretreatment serum sDR5 levels could be observed in IIIB-stage patients compared with IIIA-stage patients (P=0.009). Patients with a tumor burden >3 cm had higher pretreatment sDR5 concentration than those with a tumor burden ≤3 cm (P=0.026). Additionally, T4-stage patients had significantly higher pretreatment sDR5 levels compared with those of T1-stage patients (P<0.001). There were no significant differences between pre- and post-treatment sDR5 concentrations in the total NSCLC patient group (P=0.462), ADC subgroup (P=0.066) and SCC subgroup (P=0.052). Furthermore, when patients were divided according to therapeutic response, the pretreatment sDR5 levels in the responder patients were significantly lower compared with those of the non-responders (P<0.001). Further survival analysis showed that the patients whose pretreatment sDR5 levels were ≤14 pg/ml (cutoff value, 14 pg/ml) had a longer progression-free survival (PFS) time than patients with sDR5 levels >14 pg/ml. However, no correlation was observed between the post-treatment sDR5 levels and therapeutic response or PFS time. To the best of our knowledge, the present study results provide the first evidence that the pretreatment serum levels of sDR5 may be a useful biomarker for the diagnosis, prediction and prognosis of patients with locally advanced stage III NSCLC.