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

被引:1
作者
Wu, Jie [1 ]
Li, Lan [1 ]
Zhong, Hao [1 ]
Zhang, Hao-Han [1 ]
Li, Jing [1 ]
Zhang, Hui-Bo [1 ,2 ]
Zhao, Ya-Qi [1 ]
Xu, Bin [1 ]
Song, Qi-Bin [1 ]
机构
[1] Wuhan Univ, Canc Ctr, Renmin Hosp, Wuhan 430030, Peoples R China
[2] Tech Univ Munich, Dept Bioinformat, Wissensch Zentrum Weihenstephan, D-85354 Freising Weihenstephan, Germany
基金
中国国家自然科学基金;
关键词
kinesin superfamily 4A; cervical cancer; prognosis; chemotherapy; immunotherapy; BREAST-CANCER; CARCINOMA; ORIGIN; MYOFIBROBLASTS; TUMORS; PRC1;
D O I
10.1007/s11596-022-2636-y
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
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.
引用
收藏
页码:1273 / 1284
页数:12
相关论文
共 34 条
[1]   Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade [J].
Charoentong, Pornpimol ;
Finotello, Francesca ;
Angelova, Mihaela ;
Mayer, Clemens ;
Efremova, Mirjana ;
Rieder, Dietmar ;
Hackl, Hubert ;
Trajanoski, Zlatko .
CELL REPORTS, 2017, 18 (01) :248-262
[2]   The microtubule-associated protein PRC1 promotes early recurrence of hepatocellular carcinoma in association with the Wnt/β-catenin signalling pathway [J].
Chen, Jianxiang ;
Rajasekaran, Muthukumar ;
Xia, Hongping ;
Zhang, Xiaoqian ;
Kong, Shik Nie ;
Sekar, Karthik ;
Seshachalam, Veerabrahma Pratap ;
Deivasigamani, Amudha ;
Goh, Brian Kim Poh ;
Ooi, London Lucien ;
Hong, Wanjin ;
Hui, Kam M. .
GUT, 2016, 65 (09) :1522-1534
[3]   Mitotic phosphorylation of PRC1 at Thr470 is required for PRC1 oligomerization and proper central spindle organization [J].
Fu, Chuanhai ;
Yan, Feng ;
Wu, Fang ;
Wu, Quan ;
Whittaker, Joseph ;
Hu, Haiying ;
Hu, Renming ;
Yao, Xuebiao .
CELL RESEARCH, 2007, 17 (05) :449-457
[4]   Overexpression of chromokinesin KIF4 inhibits proliferation of human gastric carcinoma cells both in vitro and in vivo [J].
Gao, Jie ;
Sai, Ningning ;
Wang, Chengqin ;
Sheng, Xiehuang ;
Shao, Qianqian ;
Zhou, Chengjun ;
Shi, Yanqiu ;
Sun, Shanzhen ;
Qu, Xun ;
Zhu, Changjun .
TUMOR BIOLOGY, 2011, 32 (01) :53-61
[5]   Assignment of the kinesin family member 4 genes (KIF4A and KIF4B) to human chromosome bands Xq13.1 and 5q33.1 by in situ hybridization [J].
Ha, MJ ;
Yoon, J ;
Moon, E ;
Lee, YM ;
Kim, HJ ;
Kim, W .
CYTOGENETICS AND CELL GENETICS, 2000, 88 (1-2) :41-42
[6]   Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer [J].
Hoadley, Katherine A. ;
Yau, Christina ;
Hinoue, Toshinori ;
Wolf, Denise M. ;
Lazar, Alexander J. ;
Drill, Esther ;
Shen, Ronglai ;
Taylor, Alison M. ;
Cherniack, Andrew D. ;
Thorsson, Vesteinn ;
Akbani, Rehan ;
Bowlby, Reanne ;
Wong, Christopher K. ;
Wiznerowicz, Maciej ;
Sanchez-Vega, Francisco ;
Robertson, A. Gordon ;
Schneider, Barbara G. ;
Lawrence, Michael S. ;
Noushmehr, Houtan ;
Malta, Tathiane M. ;
Stuart, Joshua M. ;
Benz, Christopher C. ;
Laird, Peter W. .
CELL, 2018, 173 (02) :291-+
[7]   Subclass Mapping: Identifying Common Subtypes in Independent Disease Data Sets [J].
Hoshida, Yujin ;
Brunet, Jean-Philippe ;
Tamayo, Pablo ;
Golub, Todd R. ;
Mesirov, Jill P. .
PLOS ONE, 2007, 2 (11)
[8]   KIF4A facilitates cell proliferation via induction of p21-mediated cell cycle progression and promotes metastasis in colorectal cancer [J].
Hou, Ping-Fu ;
Jiang, Tao ;
Chen, Fang ;
Shi, Pei-Cong ;
Li, Hai-Qing ;
Bai, Jin ;
Song, Jun .
CELL DEATH & DISEASE, 2018, 9
[9]   FOXM1 promotes hepatocellular carcinoma progression by regulating KIF4A expression [J].
Hu, Guohui ;
Yan, Zhengwei ;
Zhang, Cheng ;
Cheng, Minzhang ;
Yan, Yehong ;
Wang, Yiting ;
Deng, Libin ;
Lu, Quqin ;
Luo, Shiwen .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2019, 38 (1)
[10]   Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response [J].
Jiang, Peng ;
Gu, Shengqing ;
Pan, Deng ;
Fu, Jingxin ;
Sahu, Avinash ;
Hu, Xihao ;
Li, Ziyi ;
Traugh, Nicole ;
Bu, Xia ;
Li, Bo ;
Liu, Jun ;
Freeman, Gordon J. ;
Brown, Myles A. ;
Wucherpfennig, Kai W. ;
Liu, X. Shirley .
NATURE MEDICINE, 2018, 24 (10) :1550-+