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

• Published in: Clinical cancer research Vol. 14; no. 21; pp. 6979 - 6987
• Main Authors: Chang, Kai-Ping, Hao, Sheng-Po, Chang, Jui-Hung, Wu, Chih-Ching, Tsang, Ngan-Ming, Lee, Yun-Shien, Hsu, Chen-Lung, Ueng, Shir-Hwa, Liu, Shiau-Chin, Liu, Yu-Lun, Wei, Pei-Cih, Liang, Yin, Chang, Yu-Sun, Yu, Jau-Song
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.11.2008
• Subjects: Antineoplastic agents; Biological and medical sciences; CCL20/MIP-3α; EBV; Medical sciences; Nasopharyngeal carcinoma; Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Tumor marker; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Biological fluid; Prognosis; Nasopharynx cancer; Prediction; Biological marker; Malignant tumor; Nasopharynx carcinoma; Treatment; ENT disease; Serum; Pharynx disease; Diagnosis; Detection; Predictive factor; Macrophage inflammatory protein; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-0090

Purpose: We herein examine whether macrophage inflammatory protein-3α (MIP-3α) 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-3α 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-3α on NPC cell motility were investigated by Transwell migration/invasion assays and RNA interference. Results: MIP-3α was overexpressed in NPC tumor cells. Serum MIP-3α 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-3α 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-3α, 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-3α level, EBV DNA load, and disease status. Among 155 consecutive NPC patients, subjects with pretreated MIP-3α 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-3α contributed to migration and invasion of NPC cells, which could be effectively inhibited by MIP-3α knockdown. Conclusions: MIP-3α may be a novel biomarker and prognosticator for NPC and is involved in migration and invasion of NPC cells.