HAUS5 Is A Potential Prognostic Biomarker With Functional Significance in Breast Cancer

被引:8
作者
Huang, Zhijian [1 ,2 ]
Yang, Jiasheng [3 ]
Qiu, Wenjing [3 ]
Huang, Jing [4 ]
Chen, Zhirong [5 ]
Han, Yuanyuan [6 ]
Ye, Changsheng [1 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Breast Ctr, Guangzhou, Peoples R China
[2] Fujian Med Univ Canc Hosp, Fujian Canc Hosp, Dept Breast Surg Oncol, Fuzhou, Peoples R China
[3] Anhui Univ Technol, Sch Elect & Informat Engn, Maanshan, Peoples R China
[4] Fujian Med Univ Canc Hosp, Fujian Canc Hosp, Dept Pharm, Fuzhou, Peoples R China
[5] Fujian Normal Univ, Biomed Res Ctr South China, Fuzhou, Peoples R China
[6] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biol, Kunming, Yunnan, Peoples R China
关键词
HAUS5; bioinformatics; breast cancer; biomarker; immune infiltration; prognosis; PROTEIN;
D O I
10.3389/fonc.2022.829777
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundBreast cancer (BRCA) has become the most frequently appearing, lethal, and aggressive cancer with increasing morbidity and mortality. Previously, it was discovered that the HAUS5 protein is involved in centrosome integrity, spindle assembly, and the completion of the cytoplasmic division process during mitosis. By encouraging chromosome misdivision and aneuploidy, HAUS5 has the potential to cause cancer. The significance of HAUS5 in BRCA and the relationship between its expression and clinical outcomes or immune infiltration remains unclear. MethodsPan-cancer was analyzed by TIMER2 web and the expression differential of HAUS5 was discovered. The prognostic value of HAUS5 for BRCA was evaluated with KM plotter and confirmed with Gene Expression Omnibus (GEO) dataset. Following that, we looked at the relationship between the high and low expression groups of HAUS5 and breast cancer clinical indications. Signaling pathways linked to HAUS5 expression were discovered using Gene Set Enrichment Analysis (GSEA). The relative immune cell infiltrations of each sample were assessed using the CIBERSORT algorithm and ESTIMATE method. We evaluated the Tumor Mutation Burden (TMB) value between the two sets of samples with high and low HAUS5 expression, as well as the differences in gene mutations between the two groups. The proliferation changes of BRCA cells after knockdown of HAUS5 were evaluated by fluorescence cell counting and colony formation assay. ResultHAUS5 is strongly expressed in most malignancies, and distinct associations exist between HAUS5 and prognosis in BRCA patients. Upregulated HAUS5 was associated with poor clinicopathological characteristics such as tumor T stage, ER, PR, and HER2 status. mitotic prometaphase, primary immunodeficiency, DNA replication, cell cycle related signaling pathways were all enriched in the presence of elevated HAUS5 expression, according to GSEA analysis. The BRCA microenvironment's core gene, HAUS5, was shown to be related with invading immune cell subtypes and tumor cell stemness. TMB in the HAUS5-low expression group was significantly higher than that in the high expression group. The mutation frequency of 15 genes was substantially different in the high expression group compared to the low expression group. BRCA cells' capacity to proliferate was decreased when HAUS5 was knocked down. ConclusionThese findings show that HAUS5 is a positive regulator of BRCA progression that contributes to BRCA cells proliferation. As a result, HAUS5 might be a novel prognostic indicator and therapeutic target for BRCA patients.
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页数:12
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共 40 条
[31]   The role of the augmin complex in establishing microtubule arrays [J].
Tian, Juan ;
Kong, Zhaosheng .
JOURNAL OF EXPERIMENTAL BOTANY, 2019, 70 (12) :3035-3041
[32]   Immunological hallmarks of stromal cells in the tumour microenvironment [J].
Turley, Shannon J. ;
Cremasco, Viviana ;
Astarita, Jillian L. .
NATURE REVIEWS IMMUNOLOGY, 2015, 15 (11) :669-682
[33]   Loss of expression of FANCD2 protein in sporadic and hereditary breast cancer [J].
van der Groep, Petra ;
Hoelzel, Michael ;
Buerger, Horst ;
Joenje, Hans ;
de Winter, Johan P. ;
van Diest, Paul J. .
BREAST CANCER RESEARCH AND TREATMENT, 2008, 107 (01) :41-47
[34]   GSK3 regulates epithelial-mesenchymal transition and cancer stem cell properties in triple-negative breast cancer [J].
Vijay, Geraldine Vidhya ;
Zhao, Na ;
Den Hollander, Petra ;
Toneff, Mike J. ;
Joseph, Robiya ;
Pietila, Mika ;
Taube, Joseph H. ;
Sarkar, Tapasree R. ;
Ramirez-Pena, Esmeralda ;
Werden, Steven J. ;
Shariati, Maryam ;
Gao, Ruli ;
Sobieski, Mary ;
Stephan, Clifford C. ;
Sphyris, Nathalie ;
Miura, Noayuki ;
Davies, Peter ;
Chang, Jeffrey T. ;
Soundararajan, Rama ;
Rosen, Jeffrey M. ;
Mani, Sendurai A. .
BREAST CANCER RESEARCH, 2019, 21 (1)
[35]   Breast Cancer Treatment A Review [J].
Waks, Adrienne G. ;
Winer, Eric P. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2019, 321 (03) :288-300
[36]   Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ib/II clinical trial NCT02915432 [J].
Wang, F. ;
Wei, X. L. ;
Wang, F. H. ;
Xu, N. ;
Shen, L. ;
Dai, G. H. ;
Yuan, X. L. ;
Chen, Y. ;
Yang, S. J. ;
Shi, J. H. ;
Hu, X. C. ;
Lin, X. Y. ;
Zhang, Q. Y. ;
Feng, J. F. ;
Ba, Y. ;
Liu, Y. P. ;
Li, W. ;
Shu, Y. Q. ;
Jiang, Y. ;
Li, Q. ;
Wang, J. W. ;
Wu, H. ;
Feng, H. ;
Yao, S. ;
Xu, R. H. .
ANNALS OF ONCOLOGY, 2019, 30 (09) :1479-1486
[37]   CMF-Impute: an accurate imputation tool for single-cell RNA-seq data [J].
Xu, Junlin ;
Cai, Lijun ;
Liao, Bo ;
Zhu, Wen ;
Yang, JiaLiang .
BIOINFORMATICS, 2020, 36 (10) :3139-3147
[38]   Identifying Breast Cancer-Related Genes Based on a Novel Computational Framework Involving KEGG Pathways and PPI Network Modularity [J].
Zhang, Yan ;
Xiang, Ju ;
Tang, Liang ;
Li, Jianming ;
Lu, Qingqing ;
Tian, Geng ;
He, Bin-Sheng ;
Yang, Jialiang .
FRONTIERS IN GENETICS, 2021, 12
[39]   Focus on Cdc42 in Breast Cancer: New Insights, Target Therapy Development and Non-Coding RNAs [J].
Zhang, Yu ;
Li, Jun ;
Lai, Xing-Ning ;
Jiao, Xue-Qiao ;
Xiong, Jun-Ping ;
Xiong, Li-Xia .
CELLS, 2019, 8 (02)
[40]  
Zhuang J., 2021, IEEE ACCESS, VPP, P1