Macrophage inflammatory protein-3alpha is a novel serum marker for nasopharyngeal carcinoma detection and prediction of treatment outcomes.
OBJECTIVE
We herein examine whether macrophage inflammatory protein-3alpha (MIP-3alpha) is a biomarker for nasopharyngeal carcinoma (NPC) and whether it is involved in modulating NPC cell functions.


METHODS
The study population comprises 275 NPC patients and 250 controls. MIP-3alpha levels in tissues and sera were examined by immunohistochemistry and ELISA, respectively. EBV DNA load and EBV viral capsid antigen IgA were measured by quantitative real-time PCR and immunofluorescence assay, respectively. Effects of MIP-3alpha on NPC cell motility were investigated by Transwell migration/invasion assays and RNA interference.


RESULTS
MIP-3alpha was overexpressed in NPC tumor cells. Serum MIP-3alpha levels were significantly higher in untreated patients, recurrent patients and patients with distant metastases versus non-NPC controls, patients with complete remission, and long-term disease-free patients. In the prospective cohort, serum MIP-3alpha levels were significantly higher in untreated NPC patients with advanced tumor-node-metastasis stage versus early stage and also correlated with EBV DNA load. Measurement of MIP-3alpha, EBV DNA, and viral capsid antigen IgA levels in serial serum/plasma samples from treated patients at 6-month intervals revealed a high association between MIP-3alpha level, EBV DNA load, and disease status. Among 155 consecutive NPC patients, subjects with pretreated MIP-3alpha serum levels over 65 pg/mL had worse prognoses for overall survival and distant metastasis-free survival in univariate and multivariate analysis. Additionally, cell functional assays showed that MIP-3alpha contributed to migration and invasion of NPC cells, which could be effectively inhibited by MIP-3alpha knockdown.


CONCLUSIONS
MIP-3alpha may be a novel biomarker and prognosticator for NPC and is involved in migration and invasion of NPC cells.
Chang
Kai-Ping
KP
Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital at Lin-Kou, Taoyuan, Taiwan.
Hao
Sheng-Po
SP
Chang
Jui-Hung
JH
Wu
Chih-Ching
CC
Tsang
Ngan-Ming
NM
Lee
Yun-Shien
YS
Hsu
Chen-Lung
CL
Ueng
Shir-Hwa
SH
Liu
Shiau-Chin
SC
Liu
Yu-Lun
YL
Wei
Pei-Cih
PC
Liang
Yin
Y
Chang
Yu-Sun
YS
Yu
Jau-Song
JS
D000956:Antigens, Viral / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D036022:Capsid Proteins / Q000032:analysis; D002465:Cell Movement; D054418:Chemokine CCL20 / Q000097:blood*; D004279:DNA, Viral / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000097:blood* / Q000175:diagnosis; D009362:Neoplasm Metastasis; D011379:Prognosis
D000956:Antigens, Viral; D014408:Biomarkers, Tumor; C108355:CCL20 protein, human; D036022:Capsid Proteins; D054418:Chemokine CCL20; D004279:DNA, Viral; C041788:Epstein-Barr viral capsid antigen