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Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease, and no standard treatment and validated prognostic model were established. Serum sIL-2Rα levels were measured in 94 ENKTL patients to evaluate its relationship with clinical features, treatment response, and prognosis. Serum sIL-2Rα level was 2964 ± 1613.6 ng/L in ENKTL patients, higher than in normal healthy controls (p < 0.05). Using median level (2508.5 ng/L) as cutoff, patients were divided into higher- and lower-level group (N = 47 for each). The complete remission and overall remission rate were significantly higher in lower-level group (p < 0.05). After a median follow-up time of 22.0 months, 2-year overall survival and progression-free survival rates were 60.0 and 53.0 %, respectively. Lower sIL-2Rα level significantly correlated with better progression-free survival (PFS) and overall survival (OS) (p = 0.001 and 0.002, respectively). IPI score and treatment responses after 2 cycles of chemotherapy significantly correlated with PFS and OS (p < 0.05). In a multivariate Cox regression model that included IPI score, treatment responses, and sIL-2Rα level, all three parameters were independent prognostic factors for OS (p = 0.043, 0.001, and 0.025, respectively), and the last two parameters were also independent factors for PFS (p = 0.005 and 0.005, respectively). Elevated serum sIL-2Rα level was related to poor responses to treatments and can be used as a valuable biomarker for disease activity. Moreover, serum sIL-2Rα was an independent prognostic factor for both OS and PFS. These results need to be validated in prospective trials and may support the incorporation of anti-CD25 targeted therapy into the treatment realm of ENKTL.

Delta-like ligand 4 (DLL4), one of the transmembranous Notch ligands, is upregulated at the site of tumor growth, particularly during tumor angiogenesis. Expression pattern of DLL4 in nasopharyngeal carcinoma (NPC) and the clinical and prognostic significance remain unclear. In this study, immunohistochemical analysis (IHC) was used to examine the protein level of DLL4 in NPC tissues from two independent cohorts. In the testing cohort (311 cases), we applied the X-tile program software able to assess the optimal cutoff points for biomarkers in order to accurately classify patients according to clinical outcome. In the validation cohort (113 cases), the cutoff score derived from X-title analysis was investigated to determine the association of DLL4 expression with disease-specific survival (DFS). Our results showed that high expression of DLL4 was observed in 134 of 313 (42.8 %) in the testing cohort and 58 of 113 (43.6 %) in the validation cohort. High expression of DLL4 independently predicted poorer disease-specific survival, as evidenced by univariate and multivariate analysis (P < 0.05). Moreover, DLL4 expression was significantly elevated in distant NPC metastases relative to primary NPC tumors (P = 0.001). Importantly, we found a significant positive relationship between DLL4 and vascular endothelial growth factor (VEGF) (P < 0.001). Patients with dual elevated DLL4 and VEGF expression displayed a significant overall survival disadvantage compared to those with dual low expression (P < 0.05). These findings provide evidence that high expression of DLL4 serves as an independent predictor of poor prognosis in NPC patients.