| Background:Cervical cancer is a common malignant tumor of female reproductive system mediated by human papillomavirus infection.The progress from HPV infections to cervical cancer often takes several years to more than ten years.If we can detect HPV infections or cervical precancerous lesions in time and give intervention treatment,we can effectively reduce the incidence rate of cervical cancer.In recent years,with the promotion of cervical cancer vaccine and the increase of cervical cancer screening,the incidence rate has decreased,but tthe onset age has become younger.At present,the main treatment methods for cervical cancer are surgery,radiotherapy and chemotherapy.Most patients can benefit from them,but the recurrence and metastasis rate is still high,which is the main cause of death of most patients.Therefore,we can provide a better basis for targeted therapy of cervical cancer by looking for the specific mechanism of occurrence and development of cervical cancer and the potential biomarkers for the diagnosis and treatment of early cervical cancer.HIPPO signal pathway is a highly conserved signal pathway,which was first discovered and named by the genetic chimera gene screening of Drosophila.At present,more than 30 proteins（including Drosophila and mammals）have been identified in HIPPO pathway,including upstream regulatory proteins represented by FAT4,phosphorylated kinases represented by MST1/2-SAV1 and LATS1/2-MOB1,and downstream transcription mechanisms represented by YAP/TAZ.Fat cadherin was found when studying the mutant gene of Drosophila melanogaster in the last century.As a single transmembrane protein on the cell membrane,it can regulate the HIPPO signal pathway upstream through the transmission of intracellular and extracellular signals.FAT4 in mammals is most similar to Ft of drosophila in structure and plays the role of tumor inhibition in various tumors.LATS1 is an important protein of phosphorylated kinase in HIPPO pathway and its down-regulation leads to the occurrence of a variety of tumors.Importantly,LATS1 protein is able to phosphorylate YAP at multiple sites to further regulate YAP protein stability and cytoplasmic nuclear shuttling,thereby contributing to tumor suppression.YAP is the downstream effector of HIPPO pathway and the hub of the whole signal pathway.As one of the important subtypes of YAP,YAP1 can be regulated by upstream signals.YAP is considered to be a proto-oncogene due to its ability to control the expression of target genes by combining with TEAD family members（TEADs）.HIPPO signaling pathway is often dysregulated in a variety of malignant tumors,so the related factors in HIPPO signaling pathway are considered as potential targets for the treatment of malignant tumors.Therefore,this study is aimed to study the expressions of FAT4,LATS1 and YAP1 in HIPPO signaling pathway in cervical cancer tissues,in order to provide new ideas for tumor treatment.Purpose:By detecting the expression of FAT4（Fat atypical cadherin 4）,LATS1（Large tumor suppressor gene 1）and YAP1（Yes-associated protein1）,in cervical cancer and adjacent tissues,To analyze the relationship between three kinds of proteins with clinical characteristics and the correlation of FAT4,LATS1 and YAP1.To discuss the expression and significance of HIPPO signaling pathway in cervical cancer and the therapeutic value in cervical cancer.Methods:The tissue samples were collected from 40 patients with cervical squamous cell carcinoma who underwent surgery in the second hospital of Jilin University from 2014 to 2020 and collected the clinicopathological characteristics.The expressions of FAT4,LATS1 and YAP1 in 40 cervical cancer tissues and adjacent tissues were detected by using immunohistochemistry,The rank sum test,Chi square test,Spearman correlation analysis and other statistical methods were used to analyze the expression of the three kinds of proteins,their relationship with t clinicopathological characteristics and the correlation between them.Results:1.The expression of FAT4 in adjacent tissues（positive expression rate 85.0%）was significantly higher than that in cervical cancer group（positive expression rate 40.0%）.The difference was statistically significant（Z =-4.652 P = 0.000 < 0.05）.2.The expression of LATS1 in adjacent tissues（positive expression rate 90.0%）was significantly higher than that in cervical cancer group（positive expression rate 32.5%）.The difference was statistically significant（Z =-3.814,P = 0.000 < 0.05）.3.The expression of YAP1 in cervical cancer（positive expression rate 65.0%）was higher than that in adjacent tissues（positive expression rate 50.0%）.The difference was statistically significant（Z=-2.938,P = 0.003 < 0.05）.4.The expression of FAT4 in cervical cancer tissues was correlated with the depth of infiltration（P < 0.05）,and had nothing with the age of the patients,the degree of differentiation of cervical cancer tissues,FIGO stage,vascular invasion,lymph node metastasis,and SCC（P > 0.05）.5.The expression of LATS1 in cervical cancer tissues was correlated with lymph node metastasis（P < 0.05）,and had nothing with the age of the patients,differentiation degree of cervical cancer,FIGO stage,vascular invasion,depth of invasion and SCC（P > 0.05）.6.The expression of YAP1 in cervical cancer tissues was correlated with lymph node metastasis,depth of invasion and SCC（P < 0.05）,had nothing with the age of the patients,degree of differentiation of cervical cancer,vascular invasion and FIGO stage（P > 0.05）.7.The expression of LATS1 protein and YAP1 protein was negatively correlated in cervical cancer tissues（RS =-0.386,P=0.014 < 0.05）,The expression of FAT4 protein and YAP1 protein were negatively correlated in cervical cancer tissues（RS =-0.364,P=0.021 < 0.05）.There was no significant correlation between FAT4 protein and LATS1 protein expression in cervical cancer tissues（RS =0.087,P=0.594 > 0.05）.Conclusion:1.The expression of FAT4 and LATS1 in cervical cancer tissues was lower than that in adjacent tissues,the expression of YAP1 in cervical cancer tissues was higher than that in adjacent tissues.FAT4 and LATS1 may play an inhibitory role in the process of development and incidence of cervical cancer,and YAP1 may play a promoting role in the process of development and incidence of cervical cancer.2.The expression of FAT4 was correlated with the depth of invasion of cervical cancer,LATS1 was correlated with lymph node metastasis of cervical cancer,and YAP1 was correlated with the depth of invasion,lymph node metastasis and serum squamous epithelial antigen SCC,indicating that the three proteins may play important roles in the development,progression,and metastasis of cervical cancer.3.In cervical cancer tissues,the expression of LATS1 was negatively correlated with the expression of YAP1,FAT4 was negatively correlated with the expression of YAP1,there was no correlation between the expression of FAT4 and LATS1,FAT4 may regulate HIPPO signaling pathway with multiple regulatory mechanisms in cervical cancer,and the three proteins are involved in the process of cervical carcinogenesis and development. |
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