Correlation Analysis Of S100A11 Protein With Cervical Cancer,Cervical Cancer Radiotherapy And Clinical Prognosis

BackgroundCervical cancer is the fourth most common cancer in the world.It is also a major health problem for women.Radiotherapy is the main treatment for a small number of early and most of the patients with advanced cervical cancer.It can destroy the DNA double strand structure of tumor cells or change the tumor microenvironment by damaging the cell membrane,endoplasmic reticulum,mitochondria,lysosome and other subcellular structures of tumor cells,so as to play a role in killing tumor cells.Apoptosis is the main mode of cell death caused by radiotherapy.S100A11,a member of S100 protein family,is an EF-hand Ca2 + binding protein,which is expressed in cytoplasm,nucleus and extracellular matrix of various tissues.After binding with Ca2 +,the conformation of S100A11 changed,and the hydrophobic pocket was exposed and combined with the target protein to play a biological role.Various studies have shown that S100A11 can participate in many biological processes,such as cell growth regulation,DNA damage repair,cell membrane repair,tumor development,apoptosis,inflammatory response,cell morphological changes,etc.However,the mechanism of its effect on cervical cancer and radiotherapy is not clear.PurposeTo study the effect and possible mechanism of S100A11 protein on cervical squamous cell carcinoma and radiotherapy,and to analyze the correlation between S100A11 protein and the prognosis of patients with cervical squamous cell carcinoma.Materials and methods(1)ONCOMINE database statistical analysis of S100A11 gene expression in cervical squamous cell carcinoma and normal cervical tissue;(2)ONCOMINE database statistical analysis of S100A11 gene DNA copy number and prognosis of patients with cervical squamous cell carcinoma;(3)Collect patients’ cancer tissue and normal cervical tissue in The Second Hospital of Jilin University for standardized surgery because of cervical squamous cell carcinoma,Western blot was used to detect S100A11 protein level in cervical squamous cell carcinoma and normal cervical tissue;(4)SiHa cell line and radiation-resistant SiHa cell line were treated with radiotherapy,and CCK8 was used to detect the proliferation activity of the two cell lines after radiotherapy;(5)Western blot was used to detect S100A11 protein,apoptosis related proteins Bax and Bcl-2 level in SiHa cell line and radiation-resistant SiHa cell line after radiation intervention;(6)The biological processes involved in by S100A11 and Bcl-2 were analyzed by GO enrichment of STRING database,and their protein interaction relationship was searched to explore the relationship between S100A11 protein and mitochondrial apoptosis pathway.Results(1)The statistical results of ONCOMINE database showed that the expression level of S100A11 gene in cervical squamous cell carcinoma tissue was higher than that in normal cervical tissue;(2)ONCOMINE database showed that the cervical squamous cell carcinoma patients with higher S100A11 gene copy number level in the follow-up time of more than 8 months had better prognosis than those with lower gene copy number level;(3)The results of western blot showed that S100A11 protein level in the cervical squamous cell carcinoma tissues collected was higher than that in the normal cervical tissues;(4)CCK8 results showed that the proliferation activity of radiation-resistant SiHa cells was better than that of normal SiHa cells after radiotherapy;(5)The S100A11 protein level in radiation-resistant SiHa cells was lower than that of normal SiHa cells,while the S100A11 protein level in normal SiHa cells and radiation-resistant SiHa cells were reduced after radiotherapy,especially in radiation-resistant SiHa cells.The ratio of apoptosis related protein Bcl-2 / Bax decreased significantly in normal SiHa cells,while the ratio of Bcl-2 / Bax decreased slightly or increased in radiotherapy resistant SiHa cells;(6)Go enrichment analysis showed that S100A11 and Bcl-2 were involved in many biological processes including negative regulation of cell population proliferation.Protein interaction analysis showed that S100A11 could indirectly act on Bcl-2 through BAK1 and TP53,suggesting that S100A11 may participate in the regulation of mitochondrial apoptosis pathway through BAK1 and TP53.Conclusions(1)S100A11 protein is related to the occurrence and prognosis of cervical squamous cell carcinoma;(2)S100A11 protein is related to radiotherapy resistance of cervical squamous cell carcinoma;(3)S100A11 protein participates in radiotherapy resistance of cervical squamous cell carcinoma by regulating the level of Bcl-2 / Bax;(4)S100A11 can indirectly affect Bcl-2 through BAK1 and TP53,and radiation-resistant SiHa cells can inhibit apoptosis by reducing the level of S100A11 protein to achieve radiotherapy resistance.