Bioinformatic and Experimental Analyses Reveal That KIF4A Is a Biomarker of Therapeutic Sensitivity and Predicts Prognosis in Cervical Cancer Patients  

作　　者：Jie WU Lan LI Hao ZHONG Hao-han ZHANG Jing LI Hui-bo ZHANG Ya-qi ZHAO Bin XU Qi-bin SONG 

机构地区：[1]Cancer Center,Renmin Hospital of Wuhan University,Wuhan,430030,China [2]Department of Bioinformatics,Wissenschaftszentrum Weihenstephan,Technical University of Munich,Freising,85354,Germany

出　　处：《Current Medical Science》2022年第6期1273-1284,共12页当代医学科学（英文）

基　　金：supported by grants from Wuhan University Medical Faculty Innovation Seed Fund Cultivation Project(No.TFZZ2018025);Xiao-ping CHEN Foundation for the Development of Science and Technology of Hubei Province(No.CXPJJH12000001-2020313);the National Natural Science Foundation of China(No.81670123 and No.81670144).

摘　　要：Objective This study aims to investigate the expression,prognostic value,and function of kinesin superfamily 4A(KIF4A)in cervical cancer.Methods Cervical cancer cell lines(Hela and SiHa)and TCGA data were used for experimental and bioinformatic analyses.Overall survival(OS)and progression free survival(PFS)were compared between patients with high or low KIF4A expression.Copy number variation(CNV)and somatic mutations of patients were visualized and GISTIC 2.0 was used to identify significantly altered sites.The function of KIF4A was also explored based on transcriptome analysis and validated by experimental methods.Chemotherapeutic and immunotherapeutic benefits were inferred using multiple reference databases and algorithms.Results Patients with high KIF4A expression had better OS and PFS.KIF4A could inhibit proliferation and migration and induce G1 arrest of cervical cancer cells.Higher CNV load was observed in patients with low KIF4A expression,while the group with low KIF4A expression displayed more significantly altered sites.A total of 13 genes were found to mutate more in the low KIF4A expression group,including NOTCH1 and PUM1.The analysis revealed that low KIF4A expression may indicate an immune escape phenotype,and patients in this group may benefit more from immunotherapy.With respect to chemotherapy,cisplatin and gemcitabine may respond better in patients with high KIF4A expression,while 5-fluorouracil etc.may be responded better in patients with low KIF4A expression Conclusion KIF4A is a tumor suppressor gene in cervical cancer,and it can be used as a prognostic and therapeutic biomarker in cervical cancer.

关 键 词：kinesin superfamily 4A cervical cancer PROGNOSIS chemotherapy immunotherapy 

分 类 号：R73[医药卫生—肿瘤]