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
Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital at Lin-Kou, Taoyuan, Taiwan.
Clin Cancer Res. 2008 Nov 1;14(21):6979-87. doi: 10.1158/1078-0432.CCR-08-0090.
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.
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.
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.
MIP-3alpha may be a novel biomarker and prognosticator for NPC and is involved in migration and invasion of NPC cells.
我们在此研究巨噬细胞炎性蛋白-3α（MIP-3α）是否为鼻咽癌（NPC）的生物标志物，以及它是否参与调节NPC细胞功能。
研究人群包括275例NPC患者和250例对照。分别通过免疫组织化学和酶联免疫吸附测定法检测组织和血清中的MIP-3α水平。分别通过定量实时聚合酶链反应和免疫荧光测定法测量EBV DNA载量和EBV病毒衣壳抗原IgA。通过Transwell迁移/侵袭试验和RNA干扰研究MIP-3α对NPC细胞运动性的影响。
MIP-3α在NPC肿瘤细胞中过表达。与非NPC对照、完全缓解患者和长期无病患者相比，未治疗患者、复发患者和远处转移患者的血清MIP-3α水平显著更高。在前瞻性队列中，肿瘤-淋巴结-转移晚期的未治疗NPC患者的血清MIP-3α水平显著高于早期患者，并且还与EBV DNA载量相关。对接受治疗患者每隔6个月采集的系列血清/血浆样本中的MIP-3α、EBV DNA和病毒衣壳抗原IgA水平进行测量，结果显示MIP-3α水平、EBV 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，单因素和多因素分析显示，预处理的MIP-3α血清水平超过65 pg/mL的受试者的总生存期和无远处转移生存期预后较差。此外，细胞功能试验表明，MIP-3α促进NPC细胞的迁移和侵袭，而MIP-3α基因敲低可有效抑制这种作用。
MIP-3α可能是NPC的一种新型生物标志物和预后指标，并参与NPC细胞的迁移和侵袭。
