Expression Of Human Leukocyte Antigen G In Early Stage Cervical Cancer And Pilot Study On The Immune Function

BACKGROUNDS:Cervical cancer is the most common malignant tumor in the genital tract. The human immune system is able to monitor and eliminate innate and acquired harmful components.Lack of immune function may lead to the occurrence and development of cervical cancer.HLA-G, as a member of human leukocyte antigen I ,plays a key role in immune tolerance.The expression of HLA-G is mainly in fetal-maternal interface on the extravillous cytotrophoblast. In physiological conditions, HLA-G could also be expressed in tissues such as thymus, pancreas, cornea and some of the activated monocytes. In pathological conditions, such as tumors, virus infections, autoimmune disorder, HLA-G could be expressed abnormally. Studies have confirmed that HLA-G has abnormal expression in human malignant tumors. There was a great difference in the expression of cervical cancer.HLA-G plays an important role in the occurrence and development in ovarian cancer, lung cancer, breast cancer and other malignant tumors. We hypothesize that in incidence and development of cervical cancer HLA-G also play an important role.OBJECTIVE:1. To discuss the role of HLA-G in cervical cancer with Meta-analysis.2. To detect the expression of HLA-G in cervical cancer tissues by semi quantitative method and to understand the distribution of HLA-G in cervical cancer. To investigate the relationship between HLA-G expression and clinicopathological features of cervical cancer.3. To establish cervical cell line C-33A and CaSki which express HLA-G stably and to investigate the tumor biological characteristics and immune function of HLA-G in the pathogenesis of cervical cancer.METHODS:1. Literatures about expression of HLA-G in cervical cancer were retrieved in common database. The relationship between HLA-G and clinicopathological parameters of cervical cancer was analyzed.2. The expression of HLA-G mRNA isoform and protein were measured in early cervical cancer tissues and adjacent normal tissues.3. The clinicopathological parameters of cases were collected and the relationship between HLA-G expression and clinicopathological features were analyzed.4. To package letivirus containing HLA-G 1, transfect the HLA-G1+ lentivirus into the cervical cancer cell line to express HLA-G1 stability.5. To detect the effect of HLA-G1 on the migration ability of cervical cancer cell line and on the cytotoxicity of NK-92MI cells in cervical cancer cell line. To detect mitogen activated protein kinase (MAPK) signaling pathways of cervical cancer cell line by protein chip.RESULTS:1. Meta-analysis showed HLA-G protein expression in cervical cancer was significantly higher than that in CIN and normal cervical tissues. In the FIGO stage ?/?HLA-G expression was significantly higher than that of ?/?.2. The expression levels of HLA-G mRNA isoforms were different in the early cervical cancer tissues and adjacent cancer tissues. There was no expression of HLA-G6 in either cancer tissue or adjacent tissue, and the expression of HLA-G2 and HLA-G5 were also absent in the adjacent tissues. There was no significant difference in the expression of mRNA between the cancer tissues and the adjacent tissues (P>0.05) . The expression rate of HLA-G protein in cervical cancer was 75.6% (31/41) and no expression of HLA-G was detected in adjacent tissues.3. The expression of HLA-G protein was associated with FIGO stage and histological differentiation of cervical cancer. These results suggested that HLA-G may be involved in the progression of cervical cancer.4. To establish the cervical cancer cell lines C-33A and CaSki successfully which could express HLA-G1 protein stably.5. It showed that HLA-G1 had no effect on cervical cancer cell migration by Transwell assay. But HLA-G1 could inhibit the cytotoxicity of NK-92MI cells on cervical cancer cell line.6. Seventeen types of protein of MAKP signaling pathway were detected by protein chip. There was no difference between CaSki and CaSki-HLA-G1 cell line.CONCLUSION:1. HLA-G may promote the clinical staging of cervical cancer.2. The abnormal expression of HLA-G in cervical cancer may play a role in the occurrence and development of cervical cancer.3. HLA-G had no independent effect on the migration of cervical cancer, but it had an inhibitory effect on the cytotoxicity of NK cells in the process of immune elimination. The effect of HLA-G on cercival cell may not be mediated by the MAPK signaling pathway.