Yang Cheng-Zhe, Ma Jie, Luo Qing-Qiong, Neskey David M, Zhu Dong-Wang, Liu Ying, Myers Jeffrey N, Zhang Chen-Ping, Zhang Zhi-Yuan, Zhong Lai-Ping
Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Oral Pathol Med. 2014 Jan;43(1):28-34. doi: 10.1111/jop.12091. Epub 2013 May 26.
Although molecular mechanism of growth differentiation factor 15 (GDF15) in tumorigenesis of oral squamous cell carcinoma (OSCC) is not clear, the diagnostic and prognostic value of serum GDF15 detection has been noticed. However, serum GDF15 levels in patients with oral leukoplakia and GDF15 as a potential predictive biomarker for response to induction chemotherapy in patients with OSCC have not been reported.
Pretreatment serum GDF15 concentration was detected using an enzyme-linked immunosorbent assay in 30 healthy persons, 24 patients with oral leukoplakia, and 60 patients with OSCC.
Serum GDF15 concentration was significantly higher in patients with oral leukoplakia and OSCC, compared with healthy controls (F = 13.701, df = 2, P < 0.001). From a diagnostic standpoint, a cutoff value of 346.9 ng/l of serum GDF15 concentration was calculated using receiver operating characteristic curve, with a sensitivity of 0.750, specificity of 0.867, Youden's Index of 0.617, and area under curve of 0.863. From a prognostic standpoint, patients with serum GDF15 concentration <346.9 ng/l had an improved 3-year disease-free survival rate (64.3% vs 56.5%) compared with those above 346.9 ng/l, but the difference was not statistically significant. A decreased concentration of GDF15 (<346.9 ng/l) showed a predictive trend toward an improved response to induction chemotherapy compared with elevated concentration with clinical response rates of 100% and 71.4%, respectively, but the difference was not significant.
Elevated GDF15 level may be not only a diagnostic biomarker for oral leukoplakia, but also a prognostic/predictive biomarker associated with decreased survival and diminished response to induction chemotherapy for patients with OSCC.
尽管生长分化因子15（GDF15）在口腔鳞状细胞癌（OSCC）肿瘤发生中的分子机制尚不清楚，但血清GDF15检测的诊断和预后价值已受到关注。然而，口腔白斑患者的血清GDF15水平以及GDF15作为OSCC患者诱导化疗反应的潜在预测生物标志物尚未见报道。
采用酶联免疫吸附测定法检测30名健康人、24名口腔白斑患者和60名OSCC患者治疗前血清GDF15浓度。
与健康对照组相比，口腔白斑患者和OSCC患者的血清GDF15浓度显著更高（F = 13.701，自由度 = 2，P < 0.001）。从诊断角度来看，使用受试者工作特征曲线计算出血清GDF15浓度的截断值为346.9 ng/l，灵敏度为0.750，特异性为0.867，约登指数为0.617，曲线下面积为0.863。从预后角度来看，血清GDF15浓度<346.9 ng/l的患者3年无病生存率有所提高（64.3%对56.5%），高于346.9 ng/l的患者，但差异无统计学意义。与浓度升高相比，GDF15浓度降低（<346.9 ng/l）显示出诱导化疗反应改善的预测趋势，临床反应率分别为100%和71.4%，但差异不显著。
GDF15水平升高可能不仅是口腔白斑的诊断生物标志物，也是与OSCC患者生存率降低和诱导化疗反应减弱相关的预后/预测生物标志物。
