国际肿瘤学杂志

国际肿瘤学杂志 ›› 2018, Vol. 45 ›› Issue (7): 412-418.doi: 10.3760/cma.j.issn.1673-422X.2018.07.006

• 论著 • 上一篇    下一篇

TNF-α、TNFR1、TNFR2在不同宫颈病变组织中的表达及与临床病理特征的关系

田芸,曾健,翟光宇   

  1. 300143 天津，解放军第二五四医院妇科
  • 出版日期:2018-07-08 发布日期:2018-07-31
  • 通讯作者: 翟光宇，Email: zhaiguangyu666@163.com E-mail:zhaiguangyu666@163.com

Expressions of TNF-α, TNFR1 and TNFR2 in different cervical lesions and their relationships with clinicopathological characteristics

Tian Yun, Zeng Jian, Zhai Guangyu   

  1. Department of Gynaecology, 254th Hospital of People′s Liberation Army, Tianjin 300143, China
  • Online:2018-07-08 Published:2018-07-31
  • Contact: Zhai Guangyu, Email: zhaiguangyu666@163.com E-mail:zhaiguangyu666@163.com

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摘要： 目的  探讨肿瘤坏死因子-α（TNF-α）、肿瘤坏死因子受体-1（TNFR1）、肿瘤坏死因子受体-2（TNFR2）在不同宫颈病变组织中的表达及与临床病理特征的关系。方法  选取2015年1月至2017年12月解放军第二五四医院收治的41例宫颈鳞状细胞癌（CSCC）患者（CSCC组）为研究对象，以同时期收治的49例高度鳞状上皮内病变（HSIL）患者（HSIL组）、50例子宫肌瘤患者（正常组）为对照。采用免疫组织化学法检测不同病变宫颈组织中TNF-α的阳性表达，qRT-PCR检测TNF-α、TNFR1、TNFR2的mRNA表达水平，采用Western blotting法测定TNFR1、TNFR2蛋白表达水平。分析TNF-α mRNA、TNFR1 mRNA表达水平与CSCC患者临床病理特征的关系。结果  正常组、HSIL组、CSCC组的TNF-α阳性率分别为8.0%（4/50）、59.2%（29/49）、73.2%（30/41），3组之间的阳性率比较，差异具有统计学意义（χ2=44.786，P＜0.001）；两两比较后发现，与正常组相比，HSIL组、CSCC组的阳性率较高，差异均具有统计学意义（χ2=29.175，P＜0.001；χ2=40.883，P＜0.001）；但CSCC组与HSIL组的TNF-α阳性率比较，差异无统计学意义（χ2=1.934，P=0.164）。qRT-PCR检测结果显示，正常组、HSIL组、CSCC组的TNF-α mRNA的表达量分别为1.32±0.21、3.64±0.41、7.51±1.42，3组之间的TNF-α mRNA表达量比较，差异具有统计学意义（F=655.800，P＜0.001）；两两比较后发现，与正常组相比，HSIL组、CSCC组的TNF-α mRNA表达量较高，差异具有统计学意义（t=31.747，P＜0.001；t=51.012，P＜0.001），且CSCC组的表达量也显著高于HSIL组，差异具有统计学意义（t=20.039，P＜0.001）。TNFR1 mRNA在正常组、HSIL组、CSCC组的相对表达量分别为0.42±0.13、0.89±0.21、2.23±0.46，3组之间TNFR1 mRNA的相对表达量比较，差异具有统计学意义（F=465.900，P＜0.001）；两两比较后发现，与正常组相比，HSIL组、CSCC组的TNFR1 mRNA表达量较高，差异具有统计学意义（t=13.357，P＜0.001；t=26.587，P＜0.001），且CSCC组的表达量也显著高于HSIL组，差异具有统计学意义（t=18.407，P＜0.001）。TNFR2 mRNA在正常组、HSIL组、CSCC组的表达量分别为0.38±0.14、0.41±0.11、0.44±0.12，3组之间TNFR2的表达量比较，差异无统计学意义（F=2.633，P=0.075）。Western blottting检测结果显示，TNFR1在正常组、HSIL组、CSCC组的相对表达量分别为0.84±0.18、1.95±0.21、3.38±0.73，3组之间TNFR1的表达量比较，差异具有统计学意义（F=398.000，P＜0.001）；两两比较后发现，与正常组相比，HSIL组、CSCC组的TNFR1表达强度较高，差异具有统计学意义（t=18.273，P＜0.001；t=39.894，P＜0.001），且CSCC组的表达量也显著高于HSIL组，差异具有统计学意义（t=22.357，P＜0.001）。TNRF2在正常组、HSIL组、CSCC组的表达量分别为0.98±0.15、1.02±0.17、1.07±0.21，3组之间TNFR2的表达量比较，差异无统计学意义（F=2.938，P=0.056）。蛋白检测结果与mRNA检测结果一致。CSCC组织中的TNF-α mRNA表达量与患者的肿瘤大小（t=-8.868，P＜0.001）、分化程度（t=-5.644，P＜0.001）、临床分期（t=-19.329，P＜0.001）、浸润深度（t=-11.170，P＜0.001）、淋巴结转移（t=-8.339，P＜0.001）密切相关，TNFR1 mRNA表达量也与肿瘤大小（t=-13.309，P＜0.001）、分化程度（t=-13.449，P＜0.001）、临床分期（t=-12.949，P＜0.001）、浸润深度（t=-18.124，P＜0.001）、淋巴结转移(t=-20.506，P＜0.001）密切相关。结论  在宫颈癌组织中，TNF-α、TNFR1表达异常升高，TNFR2无明显变化。TNF-α、TNFR1表达与宫颈癌恶性程度呈正相关，是宫颈组织恶变的潜在信号，有望成为新的治疗靶点。TNFR2对下游信号通路的活化作用显著弱于TNFR1。

关键词: 宫颈肿瘤, 肿瘤坏死因子&alpha, 受体, 肿瘤坏死因子

Abstract: Objective  To investigate the expressions of tumor necrosis factor-alpha (TNF-α),  tumor necrosis factor receptor (TNFR)1 and TNFR2 in different cervical lesions and their relationships with clinicopathological characteristics. Methods  Forty-one cases of cervical squamous cell carcinoma (CSCC) patients (CSCC group) treated in 254th Hospital of People′s Liberation Army from January 2015 to December 2017 were selected as the subjects. Forty-nine cases of high grde squmous intrepithelial lesion (HSIL) (HSIL group) and fifty cases of uterine myoma (normal group) were selected as control groups. The expression of TNF-α in cervical tissues of different lesions was detected by immunohistochemistry. The expressions of TNF-α mRNA, TNFR1 mRNA and TNFR2 mRNA were detected by quantificational real-time polymerase chain reaction (qRT-PCR). The expression level of TNFR1 and TNFR2 proteins are measured by Western blotting. The relationships between the expression level of TNF-α mRNA, TNFR1 mRNA and the clinicopathological characteristics of patients were analyzed. Results  The positive rates of TNF-α in the normal group, the HSIL group and the CSCC group were 8.0% (4/50), 59.2% (29/49) and 73.2% (30/41). The difference between three groups was statistically significant (χ2=44.786, P<0.001). The positive rates of the HSIL group and the CSCC group were significantly higher than that in the normal group, the difference was statistically significant (χ2=29.175, P<0.001; χ2=40.883, P<0.001), but there was no statistical difference in the positive rates of TNFα in CSCC group and HSIL group (χ2=1.934, P=0.164).The results of qRT-PCR showed that the expressions of TNF-α mRNA in normal group, HSIL group and CSCC group were 1.32±0.21, 3.64±0.41 and 7.51±1.42. The difference of TNF-α mRNA expression among three groups was statistically significant (F=655.800, P<0.001). The expressions level of TNF-α mRNA in HSIL group and CSCC group were significantly higher than that in normal group (t=31.747, P<0.001; t=51.012, P<0.001), and the expression level of CSCC group was significantly higher than that in HSIL group (t=20.039, P<0.001). The expression levels of TNFR1 mRNA in the normal group, the HSIL group and the CSCC group were 0.42±0.13, 0.89±0.21 and 2.23±0.46. The relative expression of TNFR1 mRNA between the three groups was statistically significant (F=465.900, P<0.001). The expression levels of TNFR1 mRNA in group HSIL and CSCC were significantly higher than that in normal group (t=13.357, P<0.001; t=26.587, P<0.001), and the expression level of CSCC group was significantly higher than that in HSIL group (t=18.407, P<0.001). The expression of TNFR2 mRNA in the normal group, the HSIL group and the CSCC group were 0.38±0.14, 0.41±0.11 and 0.44±0.12. There was no significant difference between three groups (F=2.633, P=0.075). Western blottting showed that the expression intensity of TNFR1 in the normal group, the HSIL group and the CSCC group were 0.84±0.18, 1.95±0.21 and 3.38±0.73, the difference was statistically significant (F=398.000, P<0.001). The expression intensity of TNFR1 in group HSIL and CSCC were significantly higher than that in normal group (t=18.273, P<0.001; t=39.894, P<0.001), and the expression in CSCC group was also significantly higher than that in group HSIL (t=22.357, P<0.001). The expression intensity of TNRF2 in normal group, HSIL group and CSCC group were 0.98±0.15, 1.02±0.17, 1.07±0.21, and the difference was not statistically significant (F=2.938, P=0.056). The results of protein detection were in accordance with the results of mRNA detection. The expression of TNF-α mRNA in the CSCC tissues was related to the size of the tumor (t=-8.868, P<0.001), the degree of differentiation (t=-5.644, P<0.001), the clinical stage (t=-19.329, P<0.001), the depth of infiltration (t=-11.170, P<0.001), and lymph node metastasis (t=-8.339, P<0.001). The expression of TNFR1 mRNA was closely related to the tumor size (t=-13.309, P<0.001), degree of differentiation (t=-13.449, P<0.001), clinical stage (t=-12.949, P<0.001), depth of infiltration (t=-18.124, P<0.001), and lymph node metastasis (t=-20.506, P<0.001). Conclusion  In cervical cancer tissues, the expression intensity of TNF-α and TNFR1 increased abnormally, while TNFR2 did not change significantly. The expressions of TNF-α and TNFR1 are positively correlated with the malignancy of cervical cancer. They are potential signals of cervical cancer and are expected to become new therapeutic targets. However, the activation of TNFR2 to downstream signaling pathway is significantly weaker than that of TNFR1.

Key words: Uterine cervical neoplasms, Tumor necrosis factor-alpha , Receptors, tumor necrosis factor