Decreased expression of the NKG2D ligand ULBP4 may be an indicator of poor prognosis in patients with nasopharyngeal carcinoma.
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.
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Yuanji
Y
Xu
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Lin
L
Zhou
Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China.|Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
Jingfeng
J
Zong
Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.|Laboratory of Immuno-Oncology, Fujian Provincial Cancer Hospital, Fuzhou, China.
Yunbin
Y
Ye
Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.|Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou, China.
Gang
G
Chen
Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.|Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou, China.
Yanping
Y
Chen
Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.|Department of Pathology, Fujian Provincial Cancer Hospital, Fuzhou, China.
Xuehong
X
Liao
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.|Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China.|Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
Qiaojuan
Q
Guo
Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China.|Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
Sufang
S
Qiu
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.|Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China.|Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
Shaojun
S
Lin
State 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.
Honglin
H
Chen
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.|Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China.|Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
Jianji
J
Pan
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002648:Child; D003602:Cytotoxicity, Immunologic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D014158:Transcription, Genetic; D055815:Young Adult
D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C488760:RAET1E protein, human
U16-binding protein 4; nasopharyngeal carcinoma; prognosis