The prognostic value of plasma soluble CD40 ligand levels in patients with nasopharyngeal carcinoma
Introduction
CD40 ligand (CD40L) is a transmembrane protein of the tumor necrosis factor family, mainly expressed on the surface of monocytes, macrophages, T cells, B cells, platelets, and endothelial cells [1], [2], [3], [4], [5]. The CD40–CD40L co-stimulatory pathway possesses an important role in the production of some cytokines like interleukin-10 and interleukin-12, which modulate antitumor responses [6], [7]. Activation of the CD40/CD40L pathway also enhances the procoagulant activity of tumor cells through an up-regulation of tissue factor expression [8], [9]. In addition, many tumor cells also express CD40 [10], [11]. It was suggested that CD40L signaling may play a crucial role in cancer occurrence and development [12], [13].
CD40L can be cleaved from the cell surface of activated T-lymphocytes and platelets, releasing a soluble CD40L (sCD40L) which is biologically active [14], [15]. sCD40L can interact with CD40, resulting in promoting inflammatory and prothrombotic responses [16], [17], [18], [19], [20], [21], [22]. Circulating sCD40L concentrations are increased in a great deal of human diseases such as acute coronary syndrome, severe sepsis and pancreatitis [23], [24], [25], [26], [27], [28], [29], [30], [31]. High sCD40L concentrations in peripheral blood have also been found in patients with pancreatic ductal adenocarcinoma and lung cancer [32], [33]. Moreover, increased serum sCD40L concentrations are reported to be associated highly with poor survival of pancreatic ductal adenocarcinoma [32]. A recent research has shown that serum sCD40L concentrations are increased in patients with nasopharyngeal carcinoma (NPC) [34]. However, at present there is a paucity of data available on the relationship between circulating sCD40L concentrations and NPC prognosis.
Section snippets
Study population
Patients with pathologically proven and previously untreated NPC were eligible for this study. Other criteria included > 18 years and receiving complete radical radiotherapy with or without chemotherapy. The exclusion criteria included previous malignant diagnoses, concurrent malignancies, secondary tumors, severe infection and systemic autoimmune disease. Finally, this study included 312 consecutive NPC patients who were recruited at Department of Otorhinolaryngology, The First Affiliated
Study population characteristics
This study recruited 312 NPC patients and 312 healthy subjects. These patients included 232 males and 80 females. Among them, 87 patients had an age of ≥ 50 years and 225 patients had an age of < 50 years. 148 patients had smoking history and 133 patients had alcohol consumption. Theses controls included 220 males and 92 females. Among them, 80 controls had an age of ≥ 50 years and 232 controls had an age of < 50 years. 135 controls had smoking history and 125 controls had alcohol consumption. There
Discussion
The main findings of the current study were that pretreatment plasma sCD40L concentrations were increased in NPC patients compared with healthy individuals; enhanced pretreatment plasma sCD40L concentrations were correlated highly with tumor classification, lymph node classification and tumor node metastasis stage; and increased pretreatment plasma sCD40L concentrations independently predicted 5-year OS, TFS, LRFS and DMFS of NPC patients using a multivariate Cox's proportional hazard analysis.
Conclusions
This study suggests that increased pretreatment plasma sCD40L levels are associated with stage progression and shorter survival time. Thus, pretreatment sCD40L level is a potential factor for predicting long-term survival of NPC patients.
Acknowledgment
This project was supported by the National Natural Science Foundation of China (Grant No. 81472210, 81472346, 81401874, 81001212), The Science and Technology Foundation of Zhejiang Province (Grant NO. 2012C33011) and the National Natural Science Foundation of Zhejiang Province (Grant No.LQ14H160009). The authors thank all staffs in Department of Otorhinolaryngology, The First Affiliated Hospital, School of Medicine, Zhejiang University (Hangzhou, China) for their technical support.
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