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