The Expression And Correlation Analysis Of FOXP3, PD-1 And PD-L1 In The Tissue Of Cervical Cancer

Backgrounds and objectivesCervical cancer is one of the most common malignant tumors in gynecology. In recent years, it has become a trend of younger age. In recent years, more and more studies have found that the occurrence, development, metastasis and prognosis of malignant tumors are closely related to the environmental factors, The tumor cells and the surrounding environment depend on each other and restrict each other. The research of cervical cancer microenvironment has attracted more and more attention. Immune surveillance is one of the most basic function of the immune system. It can identify, destroy, kill or inhibit mutant cells, and prevent the occurrence of tumors. The decrease of cervical local immune monitoring function is an important reason for the occurrence and development of cervical cancer, The tumor infiltrating lymphocytes(TIL), in particular, the decrease of the number of CD8+T cells and the immune incompetent play a key role in cervical cancer. TIL is a heterogeneous lymphocyte population that is present in the stroma of the tumor. It is mainly based on T lymphocytes.Programmed death ligand-1(PD-L1, also known as B7-H1, is in an extremely important costimulatory molecules in immune response. Programmed death receptor 1(PD-1) belongs to the subfamily of receptor CD28 / CTLA-4, expressed in activated T cells and B cells. Recently reported said, the expression of PD-L1 is abnormal in a variety of malignant tumor, The combination of high expression of PD-L1 and PD-1 inhibited the activity of peripheral lymphocytes. Thus, tumor cells can escape immune system surveillance and attack. Regulatory T cells(Tregs) is a class of cells that regulate immune resistance and immune incompetence, it is expressed highly in many human malignant tumor tissues. Its role in the occurrence and development of cervical cancer get more and more attention. Forkhead or winged helix transcription factor(FOXP3) are considered to be the most specific markers of Tregs.In the present study, we used immunohistochemical method to detect the expression of Foxp3 PD-1 and PD-L1 in normal cervix, cervical intraepithelial neoplasia, cervical cancer tissues and lymph nodes. By analyzing the correlation between the molecules with their clinicopathological features, to explore the relationship between them with the occurrence and development of cervical cancer.To provide more experimental evidence for the diagnosis and treatment of cervical cancer. Material and Methods:The expression of FOXP3, PD-1, PD-L1 in 56 cases of cervical cancer, 40 cases of cervical intraepithelial neoplasia(CIN), 18 cases of normal cervical tissues and 30 cases of cervical cancer were detected by immunohistochemical SP method.Lymph nodes were divided into three groups, LN(+) group: positive lymph node in patients with lymph node metastasis; LN(-) group : negative lymph node in patients with lymph node metastasis; LN' group : lymph node in patients without lymph node metastasis. Analysis of the role of FOXP3, PD-1, PD-L1 in the occurrence, development and metastasis of cervical cancer, and to explore its value in the diagnosis and treatment of cervical cancer. Results:1. The positive rate of FOXP3 in the cervical carcinoma group was 85.9%, the positive rate of CIN group was 82.5%, and did not express in normal cervix group, the difference was statistically significant(P < 0.05). The positive expression rate of PD-1 in cervical carcinoma was 76.6%(49/64), and it was significantly higher than that of CIN group(30%) and normal cervix group(0%), the difference was statistically significant(P < 0.05). The positive expression rate of PD-L1 in cervical cancer and CIN had no significant difference, the difference was not statistically significant(P = 0.296 > 0.05); Compared with the normal cervix, there were significant differences, and the difference was statistically significant(P < 0.05). Among them, the positive expression rate of PD-L1 in cervical cancer cells was 75%(48/64), the positive rate of tumor infiltrating lymphocyte was 56.25%(36/64).2. The positive expression rate of Foxp3 in LN(+) group and LN(-) group was Consistent and it was 40%. Foxp3 is not expressed in LN 'group, the difference is statistically significant(P < 0.05).The positive expression rate of PD-1 and PD-L1 in LN(+) group and LN(-) group was 100%, no expression in LN' group, the difference is statistically significant(P < 0.05).3. The expression of FOXP3, PD-1 and PD-L1 was not related to the age, the size of the lesion and the HPV infection or classification of the patients with cervical cancer. The difference was not statistically significant(P>0.05). But it was related to FIGO stage, histological grade and lymph node metastasis of cervical cancer, and the difference was statistically significant(P < 0.05). The positive expression rates of FOXP3, PD-1 and PD-L1 were higher than those of middle and high differentiation(-G2 G1), and the difference was statistically significant(P < 0.05); The positive expression rate of FOXP3, PD-1 and PD-L1 FIGO in patients with stage III-IV cervical cancer was significantly higher than that of I-II patients, the difference was statistically significant(P < 0.05). The expression of PD-1 and PD-L1 in LN(+)group and LN(-)group was positive, the positive expression rate of FOXP3 in LN(+)group and LN(-)group was 40%. FOXP3, PD-1 and PD-L1 is not expressed in the LN 'group, the difference is statistically significant(P < 0.05).4. The expression of PD-L1 and PD-1 in TIL was positively correlated(r=0.657), The expression of PD-L1 in cervical cancer cells was significantly positively correlated with The expression of PD-1(r=0.915). There was no significant correlation between the expression of PD-1 and FOXP3 in TIL, and there was a positive correlation between expression of FOXP3 and PD-L1(r=0.493). Conclusions:1. The high expression of FOXP3, PD-1, PD-L1 on the infiltration lymphocyte of the cervical cancer tissues, PD-L1 can also expression in cervical cancer cells, which were correlated with FIGO stage, histological grade and lymph node metastasis of cervical cancer, suggesting that they were closely related with the occurrence, development,invasion and metastasis of the tumor. FOXP3 expression is not a necessary factor for cervical cancer lymph node metastasis.2. The expression of PD-1 and PD-L1 in cervical carcinoma was positively correlated, suggesting that PD-1/PD-L1 signaling pathway plays an important role in the occurrence and development of cervical cancer.