TGF-β1及其信号通路分子在鼻咽癌中的表达及其临床意义

Expression and Clinical Significance of TGF-β1 and Its Signaling Pathway Proteins in Nasopharyngeal Carcinoma

背景与目的:转化生长因子(transforming growth factorβ,TGF-β)是一种多功能的细胞因子,在细胞生长、分化及凋亡等方面起着重要作用。本研究检测TGF-β1及其信号转导通路中的受体TGFβRⅠ、TGFβRⅡ和该通路下游的细胞内关键分子Smad4在鼻咽癌中的表达,并分析它们与鼻咽癌预后的关系。方法:应用免疫组织化学SP法检测在91例鼻咽癌组织中,TGF-β1信号转导通路中各关键分子的表达水平,并分析它们与局部复发、远处转移和生存率的关系。结果:TGF-β1、TGFβRⅠ、TGFβRⅡ和Smad4在鼻咽癌组织中的阳性率分别为69.2%、73.6%、62.6%、72.5%;TGF-β1阳性的鼻咽癌病例在Ⅰ、Ⅱ、Ⅲ、Ⅳ期中分别为0、12.7%、50.8%、36.5%,各期比较差异有统计学意义(P<0.05);TGFβRⅠ阳性率各期比较差异无统计学意义(P>0.05);TGFβRⅡ阳性率各期比较差异有统计学意义(P<0.05);Smad4阳性率各期比较差异无统计学意义(P>0.05)。TGF-β1表达阳性病例局部复发率(22.2%)与表达阴性病例(3.6%)比较差异有统计学意义(P<0.05);TGF-β1阳性病例5年生存率为63.5%,与TGF-β1阴性病例(82.1%)之间差异有统计学意义(P<0.05)。而TGFβRⅠ、TGFβRⅡ和Smad4的阳性与阴性表达病例在局部复发率和5年生存率方面差异则均无统计学意义(P>0.05)。TGF-β1信号通路中四种关键分子的阳性病例和阴性病例在远处转移率方面差异均无统计学意义(P>0.05)。结论:鼻咽癌存在TGF-β1自分泌现象。TGF-β1阳性病例局部复发率高于阴性病例,而5年生存率低于阴性病例。

BACKGROUND ＆ OBJECTIVE： Transforming growth factor β （ TGF-β） has various biological functions, and plays important roles in cell proliferation, differentiation and apoptosis. This study was to investigate the expression and clinical significance of TGF-β1 and its signaling pathway proteins （TGF-β1 receptors TGFβRⅠ and TGFβRⅡ, cytoplasmic mediator Smad4） in nasopharyngeal carcinoma （NPC）. METHODS： The expression of TGF-β1, TGFβRⅠ, TGFβRⅡ, and Smad4 in 91 specimens of NPC was detected by SP immunohistochemistry. Their correlations to local relapse, distant metastasis and survival rate of the patients were analyzed. RESULTS： The positive rates of TGF-β1, TGFβRⅠ, TGFβRⅡ and Smad4 were 69.2%, 73.6%, 62.6% and 72.5% in NPC. The differences in the positive rates of TGF-β1 （0, 12.7%, 50.8%, and 36.5%） and TGFβRⅡ （0, 15.8%, 54.4%, and 29.8%） among stageⅠ, Ⅱ, Ⅲ and Ⅳ NPC were significant （P〈0.05）. However, there was no significant difference in the expression of TGFβRⅠ and Smad4. The local relapse rate was significantly higher and 5-year overall survival rate was significantly lower in TGF-β1-positive patients than in TGF- β1-negative patients （22.2% vs. 3.6%, P〈0.05; 63.5% vs. 82.1%, P〈0.05）. All the 4 proteins had no correlation to the distant metastasis of NPC （P〉 0.05）. CONCLUSION： Autocrine TGF-β1 exists in NPC patients, which is correlated to the local relapse and survival.