Expression and Significance of TNF-α and TNFR1 in Human Cervical Squamous Cell Carcinoma Tissues
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摘要:目的
探讨不同病理类型宫颈组织中TNF-α和TNFR1的表达及其与宫颈鳞癌之间的关系。
方法应用实时定量RT-PCR法检测正常宫颈（正常组，48例）、宫颈上皮内瘤样病变（CIN组，47例）和宫颈鳞癌（SCC组，39例）组织中TNF-α和TNFR1、TNFR2 mRNA表达水平，采用免疫组织化学SP法检测TNF-α蛋白表达，Western blot法检测TNFR1、TNFR2蛋白表达，将TNF-α和TNFR1 mRNA表达结果与临床病理结果进行相关性分析。
结果TNF-α和TNFR1的mRNA表达水平随宫颈癌变程度的增加而升高，组间两两比较差异均有统计学意义（P<0.05），而TNFR2在各组中的表达差异无统计学意义（P>0.05）；TNF-α在宫颈组织中的表达随病理程度的增加有显著升高，正常组为6.25%、CIN组为58.82%、SCC组为71.79%，组间比较差异有统计学意义（P<0.01）；TNFR1蛋白表达水平随宫颈癌变程度的增加而升高，差异均有统计学意义（P<0.05），TNFR2在各组中的表达变化不明显，均与其mRNA在各组间的表达结果一致；SCC组中的TNF-α和TNFR1 mRNA的表达量与肿瘤大小、临床分期、浸润深度以及淋巴结转移情况呈正相关性，差异均有统计学意义（P<0.05），与患者年龄以及细胞分化程度无关。
结论TNF-α和TNFR1的激活与宫颈鳞癌的发生、发展相关，参与肿瘤微环境的变化，两者将有望成为治疗宫颈鳞癌的靶标。
Abstract:ObjectiveTo explore the expression of TNF-α and TNFR1 in cervix tissues with differentpathological types and their relationship with cervical squamous cell carcinoma(SCC).
MethodsRealtimeRT-PCR was performed to determine the mRNA levels of TNF-α, TNFR1, and TNFR2 in normal cervixgroup (n=48), cervical intraepithelial neoplasia (CIN) group (n=47) and SCC group (n=39). The protein levelsof TNFR1 and TNFR2 in cervical tissues were assessed by Western blot. Immunohistochemistry was used todetermine TNF-α expression in cervical tissues. The correlation of TNF-α and TNFR1 mRNA expression withcervical pathological types were also investigated.
ResultsThe mRNA levels of TNF-α and TNFR1 wereprogressively increased with the increasing grade of carcinoma (P<0.05), whereas the difference of TNFR2mRNA expression in the three groups was not statistically significant (P＞0.05). The expression of TNF-αwas also progressively increased with the increasing grade of carcinoma, and the proportion of positive cellsin normal cervix group, CIN group and SCC group were 6.25%, 58.82% and 71.79%, respectively (P<0.01).The protein level of TNFR1 was progressively increased with the increasing grade of carcinoma (P<0.01),whereas the TNFR2 expression was unchanged. Moreover, the positive correlations were found betweenTNF-α or TNFR1 mRNA levels in SCC group and tumor size, clinical stages, invasive depth, lymphaticmetastasis(P<0.05), instead of age and differentiation degree.
ConclusionThe activation of TNF-α andTNFR1 may play a critical role in the initiation and progression of cervical carcinoma by contributing to thechanges of cancer microenvironment, which are potential therapeutic targets of SCC.
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Key words:
- Cervical squamous cell carcinoma /
- TNFR1 /
- TNF-α
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图 1 实时定量RT-PCR分析不同病理类型宫颈组织中 TNF-α mRNA的表达
Figure 1 Expression of TNF-α mRNA in different pathological cervical tissues detected by real-time quantitative RT-PCR
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图 2 免疫组织化学显示TNF-α在不同病理类型宫颈组织中的表达
Figure 2 Expression of TNF-α protein in different pathologicalcervical tissues detected by immunohistochemistry method
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图 3 TNFR1、2蛋白和mRNA在不同病理类型宫颈组织中的表达
Figure 3 Expression of TNFR1,2 protein and mRNA in different pathological cervical tissues
表 2 TNF-α和TNFR1 mRNA表达与宫颈鳞癌临床病理特征的关系 (2-ΔΔCt,x±s)
Table 2 Relationship between TNF-α,TNFR1 mRNAexpression and clinicopathological features of cervicalsquamous cell carcinoma (2-ΔΔCt,x±s)
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