SOX2高表达与胸腺上皮性肿瘤患者的较短存活率显著相关

OBJECTIVES:

Thymic epithelial tumors (TET) are heterogenous tumors which are composed of thymoma (TM) and thymic carcinoma (TC). We attempted to determine differences in gene expression between TM and TC, and to determine the effect of such genes on the prognosis of patients with TET.

MATERIALS AND METHODS:

Gene expression profiles of SOX2, OCT-4, IGF-1, IGF-1R and IR mRNA transcripts in tumor tissues of TM and TC were determined using real-time PCR (RT-PCR). We constructed tissue microarray with 140 paraffin-embedded tumor tissues and performed immunohistochemistry (IHC) for IGF-1R-related signaling molecules, including SOX2, IGF-1, IGF-1R and pAKT.

应用实时PCR（RT-PCR）测定TM和TC的肿瘤组织中SOX2、OCT-4、IGF-1、IGF-1R和IR mRNA转录物的基因表达谱。我们用140个石蜡包埋的肿瘤组织构建组织微阵列，并对IGF-1R相关的信号分子进行免疫组织化学（IHC）分析，包括SOX2，IGF-1，IGF-1R和pAKT。

RESULTS:

SOX2 mRNA expression was notably higher (216-fold) in TCs than in TMs. However, there was no significant difference in expression of IGF-1, IGF-1R, OCT-4 or IR between the two tumor types. In IHC results, SOX2 (HR: 7.57, P = 0.001) and IGF-1 (HR: 9.43, P = 0.001) expression levels in TC were significantly higher than those in TM. There was a significant correlation in expression of SOX2 with IGF-1 (P = 0.021) and pAKT (P = 0.026). In univariate analysis, clinical TNM stage, WHO classification, serum LDH, expression of SOX2, IGF-1R, IGF-1 and pAKT, were significantly correlated with overall survival (OS). Multivariate analysis using a forward-selection procedure revealed that clinical N stage (HR: 4.08, P < 0.001), M stage (HR: 3.37, P = 0.001) and SOX2 expression (HR: 4.53, P = 0.010) were significantly associated with OS.

TCs中的SOX2 mRNA表达显著高于TM中的表达（216倍）。然而，两种肿瘤类型之间IGF-1、IGF-1R、OCT-4或IR的表达没有显著差异。在IHC结果中，TC中的SOX2（HR：7.57，P = 0.001）和IGF-1（HR：9.43，P = 0.001）表达水平显著高于TM中的表达水平。SOX2与IGF-1（P = 0.021）和pAKT（P = 0.026）的表达存在显著相关性。在单变量分析中，临床TNM分期、WHO分类、血清LDH、SOX2、IGF-1R、IGF-1和pAKT的表达与总体生存（OS）显著相关。使用顺向选择法的多变量分析显示临床N分期（HR：4.08，P <0.001）、M分期（HR：3.37，P = 0.001）和SOX2表达（HR：4.53，P = 0.010）与OS显著相关。

CONCLUSIONS:

SOX2 is expressed significantly higher in TC than in TM. SOX2 expression is also closely related to IGF-1 and pAKT expression. The higher expression of SOX2 is significantly associated with shorter survival in patients with TET.

KEYWORDS:

Insulin-like growth factor 1; Prognosis; Stem cells; Thymic epithelial tumor