Thymocyte selection-associated high mobility group box gene (TOX) is aberrantly over-expressed in mycosis fungoides and correlates with poor prognosis.
Thymocyte selection-associated high mobility group box gene (TOX) is aberrantly over-expressed in mycosis fungoides and correlates with poor prognosis.
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DOI：
10.18632/oncotarget.2031
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发表时间：
2014-06-30
期刊：
影响因子：
--
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Huang Y;Litvinov IV;Wang Y;Su MW;Tu P;Jiang X;Kupper TS;Dutz JP;Sasseville D;Zhou Y
真菌样肉芽肿(MF)通常模仿常见的慢性炎症性皮肤病，很难确定诊断，部分原因是缺乏表征良好的分子标志物。此前，我们发现关键的T细胞发育调节因子TOX在早期MF中异常过度表达。在目前这项涉及两个独立患者队列的多中心研究中，我们确定了全谱MF皮肤活检中TOX过度表达的发生率，并测试了TOX表达水平是否与长期临床结果相关。我们检测了113例MF活检组织中TOX的表达水平。我们发现，在两个队列中，MF活检组织的TOX基因表达均高于对照组(队列1为对照组的17.9倍，P=0.002；队列2为对照组的5.8倍，P=0.0001)。此外，较厚的皮肤病变，如斑块和肿瘤，比较薄的斑块表达更高的TOX水平。此外，TOX的过度表达使MF与对照组区别开来(曲线下面积=0.87，P<；0.0001)。最后，TOX信使核糖核酸水平高与疾病进展风险(P=0.003)和疾病特异性死亡率(P=0.008)相关。综上所述，TOX可能是提高MF诊断和预后的有用指标。
Mycosis fungoides (MF) often mimics the common chronic inflammatory skin diseases and is difficult to be diagnosed with certainty, partly because of the lack of well-characterized molecular markers. Previously, we discovered that TOX, a key T cell development regulator,was aberrantly over-expressed in early stage MF. In the current multi-center study involving two independent patient cohorts, we determined the prevalence of TOX over-expression in the full spectrum of MF skin biopsies, and tested if TOX expression levels correlated with long term clinical outcomes. We examined TOX expression levels in 113 MF biopsies. We found that the MF biopsies expressed higher TOX mRNA than the controls in both cohorts (17.9 fold in cohort 1, P = 0.002; 5.8 fold in cohort 2, P < 0.0001). In addition, thicker skin lesions such as plaques and tumors expressed even higher TOX levels than thinner patches. Further, TOX over-expression differentiated MF from the controls (area under the curve [AUC]=0.87, P < 0.0001). Finally, high TOX mRNA levels correlated with increased risks of disease progression (P = 0.003) and disease-specific mortality (P = 0.008). In conclusion, TOX may be a useful marker for improving MF diagnosis and prognostication.
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