Hub gene associated with prognosis in bladder cancer is a novel therapeutic target

被引：1
作者：
Fang, Dengpan [1 ,2 ]
He, Yuanqiao [3 ,4 ,5 ]
Yi, Yun [6 ]
Mei, Jiaqi [7 ]
Liu, Cundong [1 ]
机构：
[1] Southern Med Univ, Affiliated Hosp 3, Dept Urol, Guangzhou, Peoples R China
[2] Jianghan Univ, Hosp Wuhan 6, Affiliated Hosp, Dept Urol, Wuhan, Peoples R China
[3] Nanchang Univ, Ctr Lab Anim Sci, Nanchang, Peoples R China
[4] Jiangxi Prov Key Lab Lab Anim, Nanchang, Jiangxi, Peoples R China
[5] Nanchang Royo Biotechnol, Nanchang 330006, Peoples R China
[6] Nanchang Univ, Affiliated Hosp 2, Nanchang, Peoples R China
[7] Nanchang Univ, Clin Med Coll 1, Nanchang, Peoples R China
来源：
PEERJ | 2023年 / 11卷
关键词：
Bladder cancer; Hub gene; Prognosis; ATP CITRATE LYASE; PROLIFERATION;
D O I：
10.7717/peerj.15670
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Objective. Bladder cancer is a clinical and social conundrum due to its high incidence and recurrence rate. It is urgent to find new targets for the diagnosis and treatment of bladder cancer and improve the prognosis and survival rate of bladder cancer patients. We sought a prognosis-related gene, built related models of evaluated bladder cancer and identified the function of the hub gene in bladder cancer. Methods. We downloaded the data of bladder cancer patients from the TCGA database, and used differentially expressed genes (DEGs), copy number variation (CNV) and survival analysis to scan the hub genes associated with prognosis in bladder cancer. Then, multi-factor cox regression was used to obtain the bladder cancer prognosis correlation model. Then, we analyzed the relationship between the expression of hub gene and immune microenvironment of bladder cancer. The relationship between the expression of hub gene and prognosis in bladder cancer patients was verified by immunohistochemistry. Cell proliferation assay and drug sensitivity test in vivo were used to verify the inhibition of bladder cancer by targeted inhibitors. Results. In bladder cancer, we screened seven hub genes (ACLY, CNP, NKIRAS2, P3H4, PDIA6, VPS25 and XPO1) associated with survival. Moreover, the multifactor regression model constructed with hub gene can well distinguish the prognosis of bladder cancer. Hub gene is mostly associated with immune microenvironment. Immunohistochemical results basically confirmed the importance of XPO1 in bladder cancer. Selinexor (an inhibitor of XPO1) could effectively inhibit the proliferation of bladder cancer in the cell proliferation experiments by CCK-8 assays and it could suppress the growth of bladder cancer in mouse bladder cancer model. Conclusions. In this study, a prognostic model with seven hub genes has provided great help for the prognosis prediction of bladder cancer patients. And XPO1 is an important target affecting the prognosis of bladder cancer, and inhibition of XPO1 can effectively inhibit bladder cancer proliferation and growth.
引用
收藏
页数：17
相关论文
共 40 条
[31]   CNV-seq, a new method to detect copy number variation using high-throughput sequencing [J].
Xie, Chao ;
Tammi, Martti T. .
BMC BIOINFORMATICS, 2009, 10
[32]   Epstein-Barr virus-coded miR-BART13 promotes nasopharyngeal carcinoma cell growth and metastasis via targeting of the NKIRAS2/NF-κB pathway [J].
Xu, Yuan-Ji ;
Zhou, Rui ;
Zong, Jing-Feng ;
Lin, Wan-Song ;
Tong, Shuang ;
Guo, Qiao-Juan ;
Lin, Cheng ;
Lin, Shao-Jun ;
Chen, Yi-Xin ;
Chen, Mei-Ru ;
Chen, Hong-Lin ;
Ye, Yun-Bin ;
Pan, Jian-Ji .
CANCER LETTERS, 2019, 447 :33-40
[33]   Inferring tumour purity and stromal and immune cell admixture from expression data [J].
Yoshihara, Kosuke ;
Shahmoradgoli, Maria ;
Martinez, Emmanuel ;
Vegesna, Rahulsimham ;
Kim, Hoon ;
Torres-Garcia, Wandaliz ;
Trevino, Victor ;
Shen, Hui ;
Laird, Peter W. ;
Levine, Douglas A. ;
Carter, Scott L. ;
Getz, Gad ;
Stemke-Hale, Katherine ;
Mills, Gordon B. ;
Verhaak, Roel G. W. .
NATURE COMMUNICATIONS, 2013, 4
[34]   clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters [J].
Yu, Guangchuang ;
Wang, Li-Gen ;
Han, Yanyan ;
He, Qing-Yu .
OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY, 2012, 16 (05) :284-287
[35]   An overview of patients with urothelial bladder cancer over the past two decades: a Surveillance, Epidemiology, and End Results (SEER) study [J].
Zang, Yan ;
Li, Xiao ;
Cheng, Yifei ;
Qi, Feng ;
Yang, Ningli .
ANNALS OF TRANSLATIONAL MEDICINE, 2020, 8 (23)
[36]   P3H4 and PLOD1 expression associates with poor prognosis in bladder cancer [J].
Zhang, Junjie ;
Dong, Yang ;
Shi, Zhenduo ;
He, Houguang ;
Chen, Jiangang ;
Zhang, Shaoqi ;
Wu, Wei ;
Zhang, Qianjin ;
Han, Conghui ;
Hao, Lin .
CLINICAL & TRANSLATIONAL ONCOLOGY, 2022, 24 (08) :1524-1532
[37]   Identification of hub genes in colorectal cancer based on weighted gene co-expression network analysis and clinical data from The Cancer Genome Atlas [J].
Zhang, Yu ;
Luo, Jia ;
Liu, Zhe ;
Liu, Xudong ;
Ma, Ying ;
Zhang, Bohang ;
Chen, Yuxuan ;
Li, Xiaofeng ;
Feng, Zhiguo ;
Yang, Ningning ;
Feng, Dayun ;
Wang, Lei ;
Song, Xinqiang .
BIOSCIENCE REPORTS, 2021, 41 (07)
[38]   Misuse of RPKM or TPM normalization when comparing across samples and sequencing protocols [J].
Zhao, Shanrong ;
Ye, Zhan ;
Stanton, Robert .
RNA, 2020, 26 (08) :903-909
[39]   Identification of immune-related and autophagy-related genes for the prediction of survival in bladder cancer [J].
Zhu, Quanfeng ;
Zhang, Lingdi ;
Deng, Yaping ;
Tang, Leilei .
BMC GENOMIC DATA, 2022, 23 (01)
[40]   YTHDC1-mediated VPS25 regulates cell cycle by targeting JAK-STAT signaling in human glioma cells [J].
Zhu, Xiaolong ;
Yang, Hui ;
Zhang, Mengying ;
Wu, Xingwei ;
Jiang, Lan ;
Liu, Xiaocen ;
Lv, Kun .
CANCER CELL INTERNATIONAL, 2021, 21 (01)
1234