Tan Eng-lai, Selvaratnam G, Kananathan R, Sam Choon-kook
School of Pharmacy and Health Sciences, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
BMC Cancer. 2006 Sep 24;6:227. doi: 10.1186/1471-2407-6-227.
Nasopharyngeal carcinoma (NPC) is a common epithelial neoplasm among the Chinese populations in Southern China and South East Asia. Epstein-Barr virus (EBV) is known to be an important etiologic agent of NPC and the viral gene products are frequently detected in NPC tissues along with elevated antibody titres to the viral proteins (VCA and EA) in a majority of patients. Elevated plasma EBV DNA load is regarded as an important marker for the presence of the disease and for the monitoring of disease progression. However, other serum/plasma parameters such as the levels of certain interleukins and growth factors have also been implicated in NPC. The objectives of the present study are, 1) to investigate the correlations between plasma EBV DNA load and the levels of interleukin (IL)-6, IL-10, TGF-beta1 and SCF (steel factor) and 2) to relate these parameters to the stages of NPC and the effect of treatment.
A total of 78 untreated NPC patients were enrolled in this study. Of these, 51 were followed-up after treatment. The remaining patients had irregular or were lost to follow-up. Plasma EBV DNA was quantified using real-time quantitative PCR. The levels of plasma interleukins and growth factors were quantified using ELISA.
A significant decrease in EBV DNA load was detected in plasma of untreated NPC patients (1669 +/- 637 copies/mL; n = 51) following treatment (57 +/- 37 copies/mL, p < 0.05); n = 51). Plasma EBV DNA load was shown to be a good prognosticator for disease progression and clinical outcome in five of the follow-up patients. A significant difference in IL-6 levels was noted between the untreated patients (164 +/- 37 pg/mL; n = 51) and following treatment (58 +/- 16 pg/mL, p < 0.05; n = 51). Positive correlations between EBV DNA load and IL-10 (r(49) = 0.535, p < 0.01), between IL6 and IL-10 (r(49) = 0.474, p < 0.01) and between TGF and SCF (r(49) = 0.464, p < 0.01) were observed in patients following treatment. None of the parameters tested including IgA-VCA were associated with tumour stages.
We conclude that among the parameters investigated, EBV DNA load and IL-6 levels were promising markers for the presence of NPC and for the assessment of treatment outcome.
鼻咽癌(NPC)是中国南方和东南亚华人中常见的上皮性肿瘤。已知爱泼斯坦-巴尔病毒(EBV)是鼻咽癌的重要病因,在大多数鼻咽癌组织中经常检测到病毒基因产物,同时大多数患者体内针对病毒蛋白(VCA和EA)的抗体滴度升高。血浆EBV DNA载量升高被视为疾病存在和监测疾病进展的重要标志物。然而,其他血清/血浆参数,如某些白细胞介素和生长因子的水平也与鼻咽癌有关。本研究的目的是:1)研究血浆EBV DNA载量与白细胞介素(IL)-6、IL-10、转化生长因子-β1(TGF-β1)和干细胞因子(SCF)水平之间的相关性;2)将这些参数与鼻咽癌的分期及治疗效果相关联。
本研究共纳入78例未经治疗的鼻咽癌患者。其中,51例患者在治疗后进行了随访。其余患者随访不规律或失访。采用实时定量PCR对血浆EBV DNA进行定量。采用酶联免疫吸附测定法(ELISA)对血浆白细胞介素和生长因子水平进行定量。
未经治疗的鼻咽癌患者血浆中EBV DNA载量(1669±637拷贝/mL;n = 51)在治疗后显著降低(57±37拷贝/mL,p < 0.05;n = 51)。在5例随访患者中,血浆EBV DNA载量被证明是疾病进展和临床结局的良好预后指标。未经治疗的患者(164±37 pg/mL;n = 51)与治疗后患者(58±16 pg/mL,p < 0.05;n = 51)的IL-6水平存在显著差异。治疗后的患者中观察到EBV DNA载量与IL-10之间呈正相关(r(49) = 0.535,p < 0.01)、IL-6与IL-10之间呈正相关(r(49) = 0.474,p < 0.01)以及TGF与SCF之间呈正相关(r(49) = 0.464,p < 0.01)。包括IgA-VCA在内的所有检测参数均与肿瘤分期无关。
我们得出结论,在所研究的参数中,EBV DNA载量和IL-6水平是鼻咽癌存在及评估治疗效果的有前景的标志物。