转化生长因子β1信号传导通路在口腔鳞癌中的功能意义

Functional significance of TGF-β1 signal transduction pathway in oral squamous cell carcinoma

目的探讨转化生氏网子β1（TGF-β1）及其信号通路分子在口腔鳞癌中的表达及与口腔鳞癌发生和转移的关系。方法采用免疫组织化学SP方法，检测TGF-β1及其受体I（TβRI）、Ⅱ（TβRⅡ）和该信号内下游关键分子Smad4在10例正常口腔组织和108例口腔鳞癌组织中的表达情况，分析其与口腔鳞癌发生和转移的关系。结果TβRⅡ和Smad4在口腔鳞癌组织中的阳性表达率分别为34.3％和38.9％，在正常口腔上皮组织中的阳性表达率分别为80.0％和100.0％，差异有统计学意义（P〈0.05）；而TGF-β1、TβR1的阳性表达在口腔鳞癌组织和正常口腔上皮组织间的差异无统计学意义（P〉0.05）。TGF-β1、Smad4、TβRI和TβRⅡ的阳性表达率均与临床分期呈负相关（P〈0.01），其中TGF-β1表达与临床分期、组织分化、肿瘤发生部位有关（P〈0.05）；Smad4表达与组织分化、淋巴结转移呈负相关（P〈0.05）；虽然TβRⅡ表达与淋巴结转移无关（P〉0.05），们淋巴结转移组的TβRⅡ表达明显低于无淋巴结转移组。结论Smad4介导的TGF-β1（TGF-β1／Smad4）信号通路异常与口腔鳞癌的发生和发展密切相关，TβRⅡ、Smad4低表达可促进口腔鳞癌的转移。

Objective The aim of this study was to investigate the expression of transforming growth factor-β1（TGF-β1） and its signaling pathway molecules in oral squamous cell carcinoma （OSCC） and analyze the association between these factors and genesis and metastasis of OSCC. Methods The express of TGF-β1, TβR I , TβR Ⅱ and Smad4, a pivotal downstream molecule of its signaling, in 10 normal oral mucosa tissues and 108 OSCC was detected by SP immunohistochemistry, and thier correlation with genesis and metastasis of OSCC were assessed. Results The expressions of TβR Ⅱ and Smad4 were lower in the tumors （34.3%, 38.9% ） than those in the normal oral epithelium （80.0%, 100.0%, P 〈 0.05 ）. The positive expression rates of TGF-β1 and TβR I in the normal oral epithelium and OSCC were not significantly different（ P 〉 0.05 ）. There was an inverse correlation between TGF-β1, Smad4, TβR Ⅱ , TⅡR I expression and clinical stages （ P 〈 0.01 ）. The expression of TGF-Ⅱ1 was related with histological differentiation and tumor localization （P 〈 0.05 ）. There was a relationship beteween Smad4 expression and histological differentiation and lymph node metastasis （ P 〈 0.05 ）. The expression of TⅡR Ⅱ in the samples with lymph node metastasis was less than that in the ones without lymph node metastasis （P 〈 0.01 ）, although there was no association between expression of TβR Ⅱ and lymph node metastasis status. Conclusion There is an important relationship between the abnormal TGF-β1/Smad4 signal pathway and genesis and development of OSCC, while the low expressed Smad4 and TβR Ⅱ may promote the metastasis of OSCC.