Macrophage Inflammatory Protein-3α Is a Novel Serum Marker for Nasopharyngeal Carcinoma Detection and Prediction of Treatment Outcomes
Macrophage Inflammatory Protein-3α Is a Novel Serum Marker for Nasopharyngeal Carcinoma Detection and Prediction of Treatment Outcomes
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DOI：
10.1158/1078-0432.ccr-08-0090
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发表时间：
2008-11-01
影响因子：
11.5
通讯作者：
Yu, Jau-Song
中科院分区：
文献类型：
--
作者：
Chang, Kai-Ping;Hao, Sheng-Po;Yu, Jau-Song
目的：我们在此研究巨噬细胞炎性蛋白-3 α（MIP-3 α）是否是鼻咽癌（NPC）的生物标志物，以及它是否参与调节NPC细胞functions.Experimental Design：研究人群包括275例NPC患者和250例对照。采用免疫组化和ELISA法分别检测组织和血清中MIP-3 α的水平。采用实时荧光定量PCR和免疫荧光法分别检测E8 VDNA载量和EBV衣壳抗原伊加。结果：MIP-3 α在鼻咽癌细胞中高表达;血清MIP-3 α水平在未治疗患者、复发患者和远处转移患者中显著高于非NPC对照、完全缓解患者和长期无病患者。在前瞻性队列中，血清MIP-3 α水平在未经治疗的晚期肿瘤淋巴结转移期NPC患者中显著高于早期患者，并且与EBV DNA载量相关。以6个月为间隔，对接受治疗的患者的系列血清/血浆样本中的MIP-3 α、EBV DNA和病毒衣壳抗原伊加水平进行测量，结果显示MIP-3 α水平、E8 V DNA载量和疾病状态之间存在高度相关性。在155例连续的NPC患者中，在单因素和多因素分析中，预先治疗的MIP-3 α血清水平超过65 pg/mL的受试者的总生存率和无远处转移生存率较差。结论：MIP-3 α可能是一种新的鼻咽癌生物标志物和预测因子，参与了鼻咽癌细胞的迁移和侵袭。
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.