Macrophage Inflammatory Protein-3α Is a Novel Serum Marker for Nasopharyngeal Carcinoma Detection and Prediction of Treatment Outcomes

Purpose: We herein examine whether macrophage inflammatory protein-3 alpha (MIP-3 alpha) is a biomarker for nasopharyngeal carcinoma (NPC) and whether it is involved in modulating NPC cell functions. Experimental Design: The study population comprises 275 NPC patients and 250 controls. MIP-3 alpha levels in tissues and sera were examined by immunohistochemistry and ELISA, respectively. E8V DNA load and EBV viral capsid antigen IgA were measured by quantitative real-time PCR and immunofluorescence assay, respectively. Effects of MIP-3 alpha on NPC cell motility were investigated by Transwell migration/invasion assays and RNA interference. Results: MIP-3 alpha was overexpressed in NPC tumor cells. Serum MIP-3 alpha 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-3 alpha 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-3 alpha, 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-3 alpha level, E8V DNA load, and disease status. Among 155 consecutive NPC patients, subjects with pretreated MIP-3 alpha 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-3 alpha contributed to migration and invasion of NPC cells, which could be effectively inhibited by MIP-3 alpha knockdown. Conclusions: MIP-3 alpha may be a novel biomarker and prognosticator for NPC and is involved in migration and invasion of NPC cells.