Decreased expression of the NKG2D ligand ULBP4 may be an indicator of poor prognosis in patients with nasopharyngeal carcinoma
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Yuanji Xu1,*, Lin Zhou1,*, Jingfeng Zong2,3, Yunbin Ye3,4, Gang Chen3,5, Yanping Chen3,5, Xuehong Liao3,5, Qiaojuan Guo1,2,3, Sufang Qiu2,3, Shaojun Lin1,2,3, Honglin Chen6 and Jianji Pan1,2,3
1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
2Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China
3Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China
4Laboratory of Immuno-Oncology, Fujian Provincial Cancer Hospital, Fuzhou, China
5Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou, China
6State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology and The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China
*These authors have contributed equally to this work
Jianji Pan, email: firstname.lastname@example.org
Honglin Chen, email: email@example.com
Keywords: U16-binding protein 4, nasopharyngeal carcinoma, prognosis
Received: August 15, 2016 Accepted: December 27, 2016 Published: January 31, 2017
U16-binding protein 4 (ULBP4), a human ligand for natural killer group 2, member D (NKG2D) receptor on NK cells and subsets of T cells, is thought to activate anticancer immune responses. However, the expression pattern and prognostic effect of ULBP4 in nasopharyngeal carcinoma (NPC) has not been investigated. We first compared ULBP4 expression between archival 15 NPC tissues and 8 normal nasopharynx (NP) tissues using qPCR. Then ULBP4 expression among 111 NPC specimens was validated on immunohistochemical examination. In addition, the association of ULBP4 expression with clinical characteristics and survival outcomes was analyzed. Furthermore, the impact of ULBP4 expression in NPC cells on the cytotoxic activity of NK cells was investigated. Both mRNA and protein ULBP4 expressions of NPC tissues were significantly lower than those in normal NP tissues. However, no association of ULBP4 expression with clinical characteristics was observed. Patients with NPC having decreased expression of UBLP4 had significantly poorer overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) than those with preserved levels of ULBP4. On multivariate analyses, low expression of ULBP4 was of borderline significance for OS, PFS, and DMFS (P = 0.060, 0.053, and 0.076, respectively). Further, LDH analysis demonstrated that the cytotoxic activitity of NK cells against C666-1 or 5-8F NPC cells with lenti-ULBP4 was considerably increased as compared to those with lenti-vector at various E/T ratios. Hence, restoration of ULBP4 expression may be a novel therapeutic strategy for treatment of NPC. However, further study is required to confirm these findings.
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