Expression and significance of CDK1 based on bioinformatics in lung adenocarcinoma_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

GUO Jiadong ¹ ,  HUANG Bo ¹ , WANG Siwang ² , LIU Shaobo ¹

1. Department of Thoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, Liaoning, P.R.China;
2. Department of Cardiothoracic Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, Liaoning, P.R.China;

Corresponding author：

HUANG Bo, Email: huangbo762000@126.com

Keywords：

Cyclin-dependent kinase 1 (CDK1); lung adenocarcinoma; bioinformatics analysis; prognosis

DOI：

10.7507/1007-4848.201909003

Video：

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Objective To analyze the expression and clinical significance of cyclin-dependent kinase 1 (CDK1) in lung adenocarcinoma by bioinformatics.Methods Based on the gene expression data of lung adenocarcinoma patients in The Cancer Genome Atlas (TCGA), the differential expression of CDK1 in lung adenocarcinoma tissues and normal lung tissues was analyzed. The expression of CDK1 gene in lung adenocarcinoma was analyzed by UALCAN at different angles. Survival analysis of different levels of CDK1 gene expression in lung adenocarcinoma was performed using Kaplan-Meier Plotter. Correlation Cox analysis of CDK1 expression and overall survival was based on clinical data of lung adenocarcinoma in TCGA. Gene set enrichment analysis was performed on gene sequences related to CDK1 expression in clinical cases. The protein interaction network of CDK1 from Homo sapiens was obtained by STRING. CDK1-related gene proteins were obtained and analyzed by the web server Gene Expression Profiling Interactive Analysis (GEPIA).Results Based on the analysis of TCGA gene expression data, CDK1 expression in lung adenocarcinoma was higher than that in normal lung tissues. UALCAN analysis showed that high CDK1 expression may be associated with smoking. Survival analysis indicated that when CDK1 gene was highly expressed, patients with lung adenocarcinoma had a poor prognosis. Univariate and multivariate Cox regression analysis of CDK1 expression and overall survival showed that high CDK1 expression was an independent risk factor for survival of patients with lung adenocarcinoma. Gene set enrichment analysis revealed that high CDK1 expression was closely related to DNA replication, cell cycle, cancer pathway and p53 signaling pathway.Conclusion CDK1 may be a potential molecular marker for prognosis of lung adenocarcinoma. In addition, CDK1 regulation may play an important role in DNA replication, cell cycle, cancer pathway and p53 signaling pathway in lung adenocarcinoma.

Citation： GUO Jiadong, HUANG Bo, WANG Siwang, LIU Shaobo. Expression and significance of CDK1 based on bioinformatics in lung adenocarcinoma. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2020, 27(5): 530-538. doi: 10.7507/1007-4848.201909003 Copy

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2.	Majem M, Juan O, Insa A, et al. SEOM clinical guidelines for the treatment of non-small cell lung cancer (2018). Clin Transl Oncol, 2019, 21(1): 3-17.
3.	Petrone A, Adamo ME, Cheng C, et al. Identification of candidate cyclin-dependent kinase 1 (Cdk1) substrates in mitosis by quantitative phosphoproteomics. Mol Cell Proteomics, 2016, 15(7): 2448-2461.
4.	Santamaría D, Barrière C, Cerqueira A, et al. Cdk1 is sufficient to drive the mammalian cell cycle. Nature, 2007, 448(7155): 811-815.
5.	Yang W, Cho H, Shin HY, et al. Accumulation of cytoplasmic Cdk1 is associated with cancer growth and survival rate in epithelial ovarian cancer. Oncotarget, 2016, 7(31): 49481-49497.
6.	Ravindran Menon D, Luo Y, Arcaroli JJ, et al. CDK1 interacts with Sox2 and promotes tumor initiation in human melanoma. Cancer Res, 2018, 78(23): 6561-6574.
7.	Yang CA, Huang HY, Yen JC, et al. Prognostic value of RNASEH2A- CDK1- and CD151-related pathway gene profiling for kidney cancers. Int J Mol Sci, 2018, 19(6): 1586.
8.	Bednarek K, Kiwerska K, Szaumkessel M, et al. Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma. Tumour Biol, 2016, 37(8): 11115-11126.
9.	Li L, Qu YW, Li YP. Over-expression of miR-1271 inhibits endometrial cancer cells proliferation and induces cell apoptosis by targeting CDK1. Eur Rev Med Pharmacol Sci, 2017, 21(12): 2816-2822.
10.	Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia, 2017, 19(8): 649-658.
11.	Nagy Á, Lánczky A, Menyhárt O, et al. Author correction: validation of mirna prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep, 2018, 8(1): 11515.
12.	Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A, 2005, 102(43): 15545-15550.
13.	Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res, 2019, 47(D1): D607-D613.
14.	Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res, 2017, 45(W1): W98-W102.
15.	Zhong N, Shi S, Wang H, et al. Silencing Aurora-A with siRNA inhibits cell proliferation in human lung adenocarcinoma cells. Int J Oncol, 2016, 49(3): 1028-1038.
16.	Zheng X, Chi J, Zhi J, et al. Aurora-A-mediated phosphorylation of LKB1 compromises LKB1/AMPK signaling axis to facilitate NSCLC growth and migration. Oncogene, 2018, 37(4): 502-511.
17.	Shi R, Sun Q, Sun J, et al. Cell division cycle 20 overexpression predicts poor prognosis for patients with lung adenocarcinoma. Tumour Biol, 2017, 39(3): 1010428317692233.
18.	He X, Zhang C, Shi C, et al. Meta-analysis of mRNA expression profiles to identify differentially expressed genes in lung adenocarcinoma tissue from smokers and non-smokers. Oncol Rep, 2018, 39(3): 929-938.
19.	Chen H, Lee J, Kljavin NM, et al. Requirement for BUB1B/BUBR1 in tumor progression of lung adenocarcinoma. Genes Cancer, 2015, 6(3-4): 106-118.
20.	Song YJ, Tan J, Gao XH, et al. Integrated analysis reveals key genes with prognostic value in lung adenocarcinoma. Cancer Manag Res, 2018, 10: 6097-6108.
21.	Yan W, Yu H, Li W, et al. Plk1 promotes the migration of human lung adenocarcinoma epithelial cells via STAT3 signaling. Oncol Lett, 2018, 16(5): 6801-6807.
22.	Malumbres M. Cyclin-dependent kinases. Genome Biol, 2014, 15(6): 122.
23.	Piao J, Zhu L, Sun J, et al. High expression of CDK1 and BUB1 predicts poor prognosis of pancreatic ductal adenocarcinoma. Gene, 2019, 701: 15-22.
24.	Gheghiani L, Loew D, Lombard B, et al. Plk1 Activation in late G2 sets up commitment to mitosis. Cell Rep, 2017, 19(10): 2060-2073.
25.	Jones MC, Askari JA, Humphries JD, et al. Cell adhesion is regulated by CDK1 during the cell cycle. J Cell Biol, 2018, 217(9): 3203-3218.
26.	Deneke VE, Melbinger A, Vergassola M, et al. Waves of Cdk1 activity in S phase synchronize the cell cycle in drosophila embryos. Dev Cell, 2016, 38(4): 399-412.
27.	Gan W, Zhao H, Li T, et al. CDK1 interacts with iASPP to regulate colorectal cancer cell proliferation through p53 pathway. Oncotarget, 2017, 8(42): 71618-71629.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Majem M, Juan O, Insa A, et al. SEOM clinical guidelines for the treatment of non-small cell lung cancer (2018). Clin Transl Oncol, 2019, 21(1): 3-17.
3. Petrone A, Adamo ME, Cheng C, et al. Identification of candidate cyclin-dependent kinase 1 (Cdk1) substrates in mitosis by quantitative phosphoproteomics. Mol Cell Proteomics, 2016, 15(7): 2448-2461.
4. Santamaría D, Barrière C, Cerqueira A, et al. Cdk1 is sufficient to drive the mammalian cell cycle. Nature, 2007, 448(7155): 811-815.
5. Yang W, Cho H, Shin HY, et al. Accumulation of cytoplasmic Cdk1 is associated with cancer growth and survival rate in epithelial ovarian cancer. Oncotarget, 2016, 7(31): 49481-49497.
6. Ravindran Menon D, Luo Y, Arcaroli JJ, et al. CDK1 interacts with Sox2 and promotes tumor initiation in human melanoma. Cancer Res, 2018, 78(23): 6561-6574.
7. Yang CA, Huang HY, Yen JC, et al. Prognostic value of RNASEH2A- CDK1- and CD151-related pathway gene profiling for kidney cancers. Int J Mol Sci, 2018, 19(6): 1586.
8. Bednarek K, Kiwerska K, Szaumkessel M, et al. Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma. Tumour Biol, 2016, 37(8): 11115-11126.
9. Li L, Qu YW, Li YP. Over-expression of miR-1271 inhibits endometrial cancer cells proliferation and induces cell apoptosis by targeting CDK1. Eur Rev Med Pharmacol Sci, 2017, 21(12): 2816-2822.
10. Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia, 2017, 19(8): 649-658.
11. Nagy Á, Lánczky A, Menyhárt O, et al. Author correction: validation of mirna prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep, 2018, 8(1): 11515.
12. Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A, 2005, 102(43): 15545-15550.
13. Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res, 2019, 47(D1): D607-D613.
14. Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res, 2017, 45(W1): W98-W102.
15. Zhong N, Shi S, Wang H, et al. Silencing Aurora-A with siRNA inhibits cell proliferation in human lung adenocarcinoma cells. Int J Oncol, 2016, 49(3): 1028-1038.
16. Zheng X, Chi J, Zhi J, et al. Aurora-A-mediated phosphorylation of LKB1 compromises LKB1/AMPK signaling axis to facilitate NSCLC growth and migration. Oncogene, 2018, 37(4): 502-511.
17. Shi R, Sun Q, Sun J, et al. Cell division cycle 20 overexpression predicts poor prognosis for patients with lung adenocarcinoma. Tumour Biol, 2017, 39(3): 1010428317692233.
18. He X, Zhang C, Shi C, et al. Meta-analysis of mRNA expression profiles to identify differentially expressed genes in lung adenocarcinoma tissue from smokers and non-smokers. Oncol Rep, 2018, 39(3): 929-938.
19. Chen H, Lee J, Kljavin NM, et al. Requirement for BUB1B/BUBR1 in tumor progression of lung adenocarcinoma. Genes Cancer, 2015, 6(3-4): 106-118.
20. Song YJ, Tan J, Gao XH, et al. Integrated analysis reveals key genes with prognostic value in lung adenocarcinoma. Cancer Manag Res, 2018, 10: 6097-6108.
21. Yan W, Yu H, Li W, et al. Plk1 promotes the migration of human lung adenocarcinoma epithelial cells via STAT3 signaling. Oncol Lett, 2018, 16(5): 6801-6807.
22. Malumbres M. Cyclin-dependent kinases. Genome Biol, 2014, 15(6): 122.
23. Piao J, Zhu L, Sun J, et al. High expression of CDK1 and BUB1 predicts poor prognosis of pancreatic ductal adenocarcinoma. Gene, 2019, 701: 15-22.
24. Gheghiani L, Loew D, Lombard B, et al. Plk1 Activation in late G2 sets up commitment to mitosis. Cell Rep, 2017, 19(10): 2060-2073.
25. Jones MC, Askari JA, Humphries JD, et al. Cell adhesion is regulated by CDK1 during the cell cycle. J Cell Biol, 2018, 217(9): 3203-3218.
26. Deneke VE, Melbinger A, Vergassola M, et al. Waves of Cdk1 activity in S phase synchronize the cell cycle in drosophila embryos. Dev Cell, 2016, 38(4): 399-412.
27. Gan W, Zhao H, Li T, et al. CDK1 interacts with iASPP to regulate colorectal cancer cell proliferation through p53 pathway. Oncotarget, 2017, 8(42): 71618-71629.

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Expression and significance of CDK1 based on bioinformatics in lung adenocarcinoma

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