Serum levels of interleukin-9 correlate with negative prognostic factors in extranodal NK/T-cell lymphoma.

Jing Zhang,Cheng-Cheng Liu,Yue Lv,Liang Wang,Qi-Rong Geng,Xiao-Qin Chen,Wei-Da Wang,Masaru Katoh

doi:10.1371/journal.pone.0094637

Abstract

Interleukin-9 (IL-9) is more functionally diverse than previously expected, especially with regards to lymphomagenesis. However, the relationship between IL-9 and the clinicopathological features of extranodal NK/T-cell lymphoma is less well established. Patients with this lymphoma in Sun Yat-Sen University Cancer Center between January 2003 and March 2013 were systematically reviewed in an intention-to-treat analysis. Baseline serum IL-9 levels were determined using sandwich enzyme-linked immunosorbent assays. A total of seventy-four patients were enrolled in this study. The mean concentration of serum IL-9 for all patients was 6.48 pg/mL (range: 1.38–51.87 pg/mL). Age, B symptoms and local lymph node involvement were found to be related to high serum IL-9 levels. Patients with low IL-9 levels tended to have higher rates of complete remission. Notably, the median progression-free survival (PFS) and overall survival (OS) were longer in the low IL-9 level group than in the high IL-9 level group (PFS: 68.7 months vs. 28.3 months, P<0.001; OS: 86 months vs. 42.8 months, P = 0.001). Multivariate analysis revealed independent prognostic factors for PFS. Similarly, high IL-9 levels (P = 0.003) and old age (P = 0.007) were independently predictive of shorter OS. Serum IL-9 is closely related to several clinical features, such as age, B symptoms and local lymph node involvement. It can also be a significant independent prognostic factor for extranodal NK/T-cell lymphoma, which suggests a role for IL-9 in the pathogenesis of this disease and offers new insight into potential therapeutic strategies.

Highlights

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is more prevalent in Asia than in Western countries [1,2]
Nagato T et al reported that IL-9 was present in biopsy samples and serum from patients with Extranodal NK/T-cell lymphoma (ENKTL) and played an important role in the disease, possibly via an autocrine mechanism [6]. These results suggest that IL-9 may be associated with the clinicopathological features of ENKTL, little is known about the relationship between them
Patient characteristics and serum IL-9 content at baseline A total of seventy-four patients were enrolled in this study

Summary

Introduction

Extranodal NK/T-cell lymphoma (ENKTL) is more prevalent in Asia than in Western countries [1,2]. According to a recent large survey [3], it is the second most common lymphoma subtype in China and is only inferior to diffuse large B-cell lymphoma. It is characterized by vascular damage, zonal tumor cell death and prominent tissue necrosis. Several studies have indicated that IL-9 may promote oncogenesis during Hodgkin’s Lymphoma (HL) and large cell anaplastic lymphoma [8,9,10] in addition to its significant regulatory role in allergy and autoimmunity [11,12,13]. Dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway may be responsible for the oncogenesis of IL-9 in vitro and in vivo [14,15,16]

Methods

Results

Conclusion