Identification of <i>PLK4</i> as a key prognostic gene in breast cancer by bioinformatics analysis

XU Jiawei; CHEN Yuqiu; WANG Wenyi; GU Jun

doi:10.7619/jcmp.20213104

Journal of Clinical Medicine in Practice > 2021 > 25(23): 69-76, 81. > DOI: 10.7619/jcmp.20213104

XU Jiawei, CHEN Yuqiu, WANG Wenyi, GU Jun. Identification of PLK4 as a key prognostic gene in breast cancer by bioinformatics analysis[J]. Journal of Clinical Medicine in Practice, 2021, 25(23): 69-76, 81. DOI: 10.7619/jcmp.20213104

Citation:

PDF (5856 KB)

Identification of PLK4 as a key prognostic gene in breast cancer by bioinformatics analysis

1.
Institute of General Surgery of the Chinese People's Liberation Army, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu, 210000
2.
Institute of General Surgery of the Chinese People's Liberation Army, Jinling Hospital Affiliated to Medical College of Nanjing University, Nanjing, Jiangsu, 210000
3.
Institute of General Surgery of the Chinese People's Liberation Army, General Hospital of Eastern Theater of Operations of the People's Liberation Army, Nanjing, Jiangsu, 210000

More Information

Received Date: August 01, 2021
Available Online: December 20, 2021
Published Date: December 14, 2021

Graphical Abstract

Abstract

Abstract

Objective To explore the biological role and prognostic value of Polo-like kinase 4 (PLK4) in breast cancer and its influence on local immune microenvironment by bioinformatics analysis.
Methods The expression levels of PLK4 in a variety of tumors were mined through the Oncomine database. The differences in PLK4 expression in breast cancer tissues and normal tissues were retrieved by the GEPIA database and the HPA database. The correlations between PLK4 expression levels and clinical characters as well as immune infiltration in breast cancer patients were analyzed by the UALCAN database and the TIMER database respectively. The K-M plotter database was used to evaluate the prognostic value of PLK4 in breast cancer. Coexpedia database was used to construct the co-expressed gene network of PLK4 in breast cancer, and the functions of PLK4 and its key genes were analyzed by David database.
Results Both PLK4 mRNA and protein expression were significantly up-regulated in breast cancer tissues, especially in differences of P53 mutant and triple-negative breast cancers (P < 0.05), and high PLK4 expression indicated a worse prognosis. PLK4 was positively correlated with immune cell expression in the immune microenvironment of breast cancer. Twenty-five key genes of PLK4 were screened, including TPX2, CCNB2, CCNB1, BIRC5, CDC20, FOXM1 and etc, and their biological functions were mainly correlated with cell division, cell cycle, cell proliferation, ubiquitination modification and etc. KEGG pathway enrichment analysis showed that PLK4 was associated with P53 signaling pathway, FoxO signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, etc.
Conclusion The high expression of PLK4 in breast cancer tissues may indicate a poor prognosis, and it affects the immune microenvironment of breast cancer and shows the characteristics of oncogenes to a certain extent, so it might be used as a predictive indicator for the treatment of breast cancer, and is expected to become a new target for clinical diagnosis and treatment for breast cancer.
- breast cancer,
- Polo-like kinase 4,
- bioinformatics,
- tumors,
- gene regulation

FullText(HTML)

References (39)

References

[1]	World Health Organization. Latest global cancer data: cancer burden rises to 19.3 million new cases and 10.0 million cancer deaths in 2020[EB/OL]. https://www.iarc.fr/fr/news-events/latest-global-cancer-data-cancer-burden-rises-to-19-3-million-new-cases-and-10-0-million-cancer-deaths-in-2020/.
[2]	LEMANSKI C, BOURGIER C, DRAGHICI R, et al. Intraoperative partial irradiation for highly selected patients with breast cancer: Results of the INTRAOBS prospective study[J]. Cancer Radiother, 2020, 24(2): 114-119. doi: 10.1016/j.canrad.2020.01.007
[3]	ZITOUNI S, NABAIS C, JANA S C, et al. Polo-like kinases: structural variations lead to multiple functions[J]. Nat Rev Mol Cell Biol, 2014, 15(7): 433-452. doi: 10.1038/nrm3819
[4]	UEDA A, OIKAWA K, FUJITA K, et al. Therapeutic potential of PLK1 inhibition in triple-negative breast cancer[J]. Lab Invest, 2019, 99(9): 1275-1286. doi: 10.1038/s41374-019-0247-4
[5]	QIAN Y Z, HUA E, BISHT K, et al. Inhibition of Polo-like kinase 1 prevents the growth of metastatic breast cancer cells in the brain[J]. Clin Exp Metastasis, 2011, 28(8): 899-908. doi: 10.1007/s10585-011-9421-9
[6]	PITT J J, RIESTER M, ZHENG Y, et al. Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features[J]. Nat Commun, 2018, 9(1): 4181. doi: 10.1038/s41467-018-06616-0
[7]	段佳君, 邹天宁, 张季, 等. ER阳性乳腺癌中Efp和Plk3蛋白表达相关性探讨[J]. 中国癌症杂志, 2016, 26(10): 848-853.
[8]	MANO R, DUZGOL C, GANAT M, et al. Somatic mutations as preoperative predictors of metastases in patients with localized clear cell renal cell carcinoma-An exploratory analysis[J]. Urol Oncol, 2021, 39(11): e17-e24.
[9]	LI Z, DAI K, WANG C, et al. Expression of polo-like kinase 4(PLK4) in breast cancer and its response to taxane-based neoadjuvant chemotherapy[J]. J Cancer, 2016, 7(9): 1125-1132. doi: 10.7150/jca.14307
[10]	NABAIS C, PESSOA D, DE-CARVALHO J, et al. PLK4 triggers autonomous de novo centriole biogenesis and maturation[J]. J Cell Biol, 2021, 220(5): e202008090. doi: 10.1083/jcb.202008090
[11]	LEE K S, PARK J E, IL AHN J, et al. A self-assembled cylindrical platform for PLK4-induced centriole biogenesis[J]. Open Biol, 2020, 10(8): 200102. doi: 10.1098/rsob.200102
[12]	TANG Z, LI C, KANG B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses[J]. Nucleic Acids Res, 2017, 45(w1): W98-W102. doi: 10.1093/nar/gkx247
[13]	UHLÉN M, FAGERBERG L, HALLSTRÖM B M, et al. Proteomics. Tissue-based map of the human proteome[J]. Science, 2015, 347(6220): 1260419. doi: 10.1126/science.1260419
[14]	LI T W, FU J X, ZENG Z X, et al. TIMER2. 0 for analysis of tumor-infiltrating immune cells[J]. Nucleic Acids Res, 2020, 48(W1): W509-W514. doi: 10.1093/nar/gkaa407
[15]	YANG S, KIM C Y, HWANG S, et al. COEXPEDIA: exploring biomedical hypotheses via co-expressions associated with medical subject headings (MeSH)[J]. Nucleic Acids Res, 2017, 45(d1): D389-D396. doi: 10.1093/nar/gkw868
[16]	CHEN X W, ZHANG D W, JIANG F, et al. Prognostic prediction using a stemness index-related signature in a cohort of gastric cancer[J]. Front Mol Biosci, 2020, 7: 570702. doi: 10.3389/fmolb.2020.570702
[17]	ZENG Y, LI N H, LIU W, et al. Analyses of expressions and prognostic values of Polo-like kinases in non-small cell lung cancer[J]. J Cancer Res Clin Oncol, 2020, 146(10): 2447-2460. doi: 10.1007/s00432-020-03288-6
[18]	KIM D H, AHN J S, HAN H J, et al. Cep131 overexpression promotes centrosome amplification and colon cancer progression by regulating PLK4 stability[J]. Cell Death Dis, 2019, 10(8): 570. doi: 10.1038/s41419-019-1778-8
[19]	BAO J, YU Y, CHEN J N, et al. MiR-126 negatively regulates PLK-4 to impact the development of hepatocellular carcinoma via ATR/CHEK1 pathway[J]. Cell Death Dis, 2018, 9(10): 1045. doi: 10.1038/s41419-018-1020-0
[20]	ZHAO Y, WANG X. PLK4: a promising target for cancer therapy[J]. J Cancer Res Clin Oncol, 2019, 145(10): 2413-2422. doi: 10.1007/s00432-019-02994-0
[21]	ABREU P, IVANICS T, JIANG K R, et al. Novel biomarker for hepatocellular carcinoma: high tumoral PLK-4 expression is associated with better prognosis in patients without microvascular invasion[J]. HPB (Oxford), 2021, 23(3): 359-366. doi: 10.1016/j.hpb.2020.07.003
[22]	KAWAKAMI M, MUSTACHIO L M, ZHENG L, et al. Polo-like kinase 4 inhibition produces polyploidy and apoptotic death of lung cancers[J]. PNAS, 2018, 115(8): 1913-1918. doi: 10.1073/pnas.1719760115
[23]	KAZAZIAN K, GO C, WU H, et al. PLK4 promotes cancer invasion and metastasis through Arp2/3 complex regulation of the actin cytoskeleton[J]. Cancer Res, 2017, 77(2): 434-447. doi: 10.1158/0008-5472.CAN-16-2060
[24]	ROSARIO C O, KAZAZIAN K, ZIH F S, et al. A novel role for PLK4 in regulating cell spreading and motility[J]. Oncogene, 2015, 34(26): 3441-3451. doi: 10.1038/onc.2014.275
[25]	MORRIS E J, KAWAMURA E, GILLESPIE J A, et al. Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1[J]. Nat Commun, 2017, 8: 15289. doi: 10.1038/ncomms15289
[26]	LI Z H, DAI K, WANG C J, et al. Expression of polo-like kinase 4(PLK4) in breast cancer and its response to taxane-based neoadjuvant chemotherapy[J]. J Cancer, 2016, 7(9): 1125-1132. doi: 10.7150/jca.14307
[27]	ZHANG Y, TIAN J, QU C, et al. A look into the link between centrosome amplification and breast cancer[J]. Biomed Pharmacother, 2020, 132: 110924. doi: 10.1016/j.biopha.2020.110924
[28]	DENU R A, ZASADIL L M, KANUGH C, et al. Centrosome amplification induces high grade features and is prognostic of worse outcomes in breast cancer[J]. BMC Cancer, 2016, 16: 47. doi: 10.1186/s12885-016-2083-x
[29]	OGDEN A, RIDA P C G, ANEJA R. Centrosome amplification: a suspect in breast cancer and racial disparities[J]. Endocr Relat Cancer, 2017, 24(9): T47-T64. doi: 10.1530/ERC-17-0072
[30]	VITRE B, HOLLAND A J, KULUKIAN A, et al. Chronic centrosome amplification without tumorigenesis[J]. PNAS, 2015, 112(46): E6321-E6330. doi: 10.1073/pnas.1519388112
[31]	PRESS M F, XIE B, DAVENPORT S, et al. Role for polo-like kinase 4 in mediation of cytokinesis[J]. Proc Natl Acad Sci USA, 2019, 116(23): 11309-11318. doi: 10.1073/pnas.1818820116
[32]	TANG J N, LUO Y W, TIAN Z L, et al. TRIM11 promotes breast cancer cell proliferation by stabilizing estrogen receptor Α[J]. Neoplasia, 2020, 22(9): 343-351. doi: 10.1016/j.neo.2020.06.003
[33]	LIU Z, ZHANG J, XU J, et al. RNF168 facilitates oestrogen receptor ɑ transcription and drives breast cancer proliferation[J]. J Cell Mol Med, 2018, 22(9): 4161-4170. doi: 10.1111/jcmm.13694
[34]	MARINA M. Nek2 and PLK4: prognostic markers, drivers of breast tumorigenesis and drug resistance[J]. Front Biosci, 2014, 19(2): 352. doi: 10.2741/4212
[35]	KONG X Y, ZHANG K, WANG X Y, et al. Mechanism of trastuzumab resistance caused by HER-2 mutation in breast carcinomas[J]. Cancer Manag Res, 2019, 11: 5971-5982. doi: 10.2147/CMAR.S194137
[36]	DE OLIVEIRA TAVEIRA M, NABAVI S, WANG Y, et al. Genomic characteristics of trastuzumab-resistant Her2-positive metastatic breast cancer[J]. J Cancer Res Clin Oncol, 2017, 143(7): 1255-1262. doi: 10.1007/s00432-017-2358-x
[37]	CHAKRABARTY A, BHOLA N E, SUTTON C, et al. Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors[J]. Cancer Res, 2013, 73(3): 1190-1200. doi: 10.1158/0008-5472.CAN-12-2440
[38]	PEAKE B F, NAHTA R. Resistance to HER2-targeted therapies: a potential role for FOXM1[J]. Breast Cancer Manag, 2014, 3(5): 423-431. doi: 10.2217/bmt.14.33
[39]	VARGAS-RONDÓN N, PÉREZ-MORA E, VILLEGAS V E, et al. Role of chromosomal instability and clonal heterogeneity in the therapy response of breast cancer cell lines[J]. Cancer Biol Med, 2020, 17(4): 970-985. doi: 10.20892/j.issn.2095-3941.2020.0028

[1]	PU Meizhi, FENG Xiaoke, XIE Liqun. Mechanism of Xiaochaihutang in treating gastroesophageal reflux disease with insomnia based on network pharmacology[J]. Journal of Clinical Medicine in Practice, 2023, 27(9): 111-118. DOI: 10.7619/jcmp.20230405
[2]	CAI Chuanyun, JIANG Wei, HU Xin. Research progress in treatment of chronic insomnia in the elderly[J]. Journal of Clinical Medicine in Practice, 2023, 27(3): 140-143,148. DOI: 10.7619/jcmp.20222374
[3]	LI Jia, WANG Lin, LIU Nan, WANG Ting, ZHAO Xiaoya, GAO Lini, ZHAO Ping. Effect of mindfulness training on sleep quality and psychological state of perimenopausal patients with insomnia[J]. Journal of Clinical Medicine in Practice, 2022, 26(23): 85-88. DOI: 10.7619/jcmp.20222790
[4]	SHI Yan, WANG Yuanyuan, LIU Xuedong, BAI Ya, MA Lei, LI Wen. Effect of sleep restriction therapy in patients with insomnia disorder comorbid to Parkinson's disease[J]. Journal of Clinical Medicine in Practice, 2021, 25(23): 49-52. DOI: 10.7619/jcmp.20214395
[5]	ZHANG Lei, LIU Yanwei, BAO Qingxia, FENG Guoqin. Effect of auricular acupoint seed-embedding combined with Limian Plaster on long-term improvement of insomnia in patients with advanced cancer[J]. Journal of Clinical Medicine in Practice, 2021, 25(8): 64-66. DOI: 10.7619/jcmp.20210024
[6]	XUAN Jianzong, FENG Xingwen, WU Liangliang, LIU Yuan. Effect observation of Guipi Decoction combined with auricular pressing with pills in treatment of hemodialysis patients with insomnia[J]. Journal of Clinical Medicine in Practice, 2021, 25(7): 59-62. DOI: 10.7619/jcmp.20210328
[7]	ZHU Jinya, LI Yuhua. Effect of exercise therapy in treatment of patients with chronic schizophrenia accompanied by insomnia[J]. Journal of Clinical Medicine in Practice, 2020, 24(24): 57-60. DOI: 10.7619/jcmp.202024017
[8]	CAO Yin, GAO Yanfei, ZHANG Qiaoyang, ZHANG Yi. Effect of cognitive behavioral therapy for insomnia in esophageal cancer patients with insomnia[J]. Journal of Clinical Medicine in Practice, 2019, 23(10): 22-24,28. DOI: 10.7619/jcmp.201910007
[9]	HU Wenzhe, ZHANG Bo. Effect of psychological intervention for insomnia patients with traumatic brain injury in rehabilitation period[J]. Journal of Clinical Medicine in Practice, 2018, (8): 1-3. DOI: 10.7619/jcmp.201808001
[10]	GAO Lini. Effect of nursing intervention on quality of sleep and quality of life in perimenopausal women with insomnia[J]. Journal of Clinical Medicine in Practice, 2015, (18): 78-80. DOI: 10.7619/jcmp.201518025

Cited By

Cited by

Periodical cited type(5)

1.	洪玫，段宏宪，杨敏. 清肝化湿活血汤联合复方甘草酸苷片治疗酒精性肝病的临床疗效及对患者肝功能的影响. 医药论坛杂志. 2023(02): 87-89+93 .
2.	王箭焱. 舒肝宁注射液联合复方甘草酸苷对非酒精性脂肪性肝炎患者脂代谢、肝功能的影响. 中国医学创新. 2023(22): 45-48 .
3.	陈凯，孟祥林. 多烯磷脂酰胆碱注射液对自身免疫性肝炎患者肝功能指标的影响. 中国药物与临床. 2023(10): 665-669 .
4.	罗萍，蒋玲，刘杨武. 甘草酸制剂治疗病毒性肝炎的效果观察. 继续医学教育. 2022(04): 145-148 .
5.	李斌，王磊. 舒肝消癖颗粒联合复方甘草酸苷片治疗非酒精性脂肪肝的临床效果及对肝功能的影响. 反射疗法与康复医学. 2022(07): 8-10 .

Other cited types(1)

Get Citation

PDF

XML

Article views (359) PDF downloads (27) Cited by(6)

Turn off MathJax

Article Contents

Abstract

References

Identification of PLK4 as a key prognostic gene in breast cancer by bioinformatics analysis