Effects of centromere protein F expression on biological behavior and prognosis of non-small cell lung cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

CHANG Yanxiang , JIN Lei , BAI Xiongxiong , LIU Hao ,  XU Shuonan

Department of Cardiothoracic Surgery, First Affiliated Hospital of Xi'an Medical University, Xi'an, 710077, P. R. China;

Corresponding author：

XU Shuonan, Email: xsn101506@163.com

Keywords：

Non-small cell lung cancer; centromere protein F; bioinformatics; cell cycle

DOI：

10.7507/1007-4848.202012011

Video：

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Objective To investigate the expression and biological function of centromere protein F (CENPF) in non-small cell lung cancer (NSCLC) and the association with prognosis.Methods Through retrieving and analyzing the bioinformatics data such as Oncomine database, Human Protein Atlas (HPA), Kaplan-Meier Plotter, STRING and DAVID database, the expression of CENPF in both normal tissues and cancer tissues of lung cancer patients was identified, and the protein interaction network analysis, functional annotation and pathway analysis of CENPF with its associated genes were carried out.Results CENPF was overexpressed in lung adenocarcinoma tissues, but not in normal tissues. The median overall survival (OS) of NSCLC patients with low expression of CENPF was significantly longer than that of patients with high expression of CENPF. Further sub-analysis showed that low expression group from lung adenocarcinoma patients had longer median disease-free survival and OS compared with high expression group patients. CENPF and its associated hub genes mainly affected the protein K11-linked ubiquitination in biological process, anaphase-promoting complex (APC) in cell composition, ATP binding in molecular function, and cell cycle in KEGG pathway.Conclusion CENPF is regulated in tumorigenesis and progression of NSCLC, and its protein expression level has the value of early diagnosis and prognosis evaluation in lung adenocarcinoma. It is suggested that CENPF gene can be a potential target for molecular targeted therapy of NSCLC.

Citation： CHANG Yanxiang, JIN Lei, BAI Xiongxiong, LIU Hao, XU Shuonan. Effects of centromere protein F expression on biological behavior and prognosis of non-small cell lung cancer. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2022, 29(6): 711-716. doi: 10.7507/1007-4848.202012011 Copy

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2.	Zhang XC, Wang J, Shao GG, et al. Comprehensive genomic and immunological characterization of Chinese non-small cell lung cancer patients. Nat Commun, 2019, 10(1): 1772.
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5.	Rattner JB, Rao A, Fritzler MJ, et al. CENP-F is a.ca 400 kDa kinetochore protein that exhibits a cell-cycle dependent localization. Cell Motil Cytoskeleton, 1993, 26(3): 214-226.
6.	Sang M, Wu M, Meng L, et al. Identification of epithelial-mesenchymal transition-related circRNA-miRNA-mRNA ceRNA regulatory network in breast cancer. Pathol Res Pract, 2020, 216(9): 153088.
7.	An F, Zhang Z, Xia M. Functional analysis of the nasopharyngeal carcinoma primary tumorassociated gene interaction network. Mol Med Rep, 2015, 12(4): 4975-4980.
8.	Koon N, Schneider-Stock R, Sarlomo-Rikala M, et al. Molecular targets for tumour progression in gastrointestinal stromal tumours. Gut, 2004, 53(2): 235-240.
9.	Li R, Wang X, Zhao X, et al. Centromere protein F and Forkhead box M1 correlation with prognosis of non-small cell lung cancer. Oncol Lett, 2020, 19(2): 1368-1374.
10.	Sun CC, Li SJ, Hu W, et al. Comprehensive analysis of the expression and prognosis for E2Fs in human breast cancer. Mol Ther, 2019, 27(6): 1153-1165.
11.	Yang X, Zhu S, Li L, et al. Identification of differentially expressed genes and signaling pathways in ovarian cancer by integrated bioinformatics analysis. Onco Targets Ther, 2018, 11: 1457-1474.
12.	Shang S, Wang L, Su Y, et al. Local therapy combined with chemotherapy versus chemotherapy for postoperative oligometastatic non-small-cell lung cancer. Future Oncol, 2019, 15(14): 1593-1603.
13.	Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature, 2018, 553(7689): 446-454.
14.	Ko EC, Raben D, Formenti SC. The integration of radiotherapy with immunotherapy for the treatment of non-small cell lung cancer. Clin Cancer Res, 2018, 24(23): 5792-5806.
15.	宁晔, 谢冬, 佘云浪, 等. 2020版NCCN肺癌筛查指南解读. 中国胸心血管外科临床杂志, 2020, 27(3): 251-254.
16.	Wu SG, Shih JY. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer, 2018, 17(1): 38.
17.	Yu B, Chen L, Zhang W, et al. TOP2A and CENPF are synergistic master regulators activated in cervical cancer. BMC Med Genomics, 2020, 13(1): 145.
18.	Sun J, Huang J, Lan J, et al. Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer. Cancer Cell Int, 2019, 19: 264.
19.	Aytes A, Mitrofanova A, Lefebvre C, et al. Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy. Cancer Cell, 2014, 25(5): 638-651.
20.	Shahid M, Lee MY, Piplani H, et al. Centromere protein F (CENPF), a microtubule binding protein, modulates cancer metabolism by regulating pyruvate kinase M2 phosphorylation signaling. Cell Cycle, 2018, 17(24): 2802-2818.
21.	Cai C, Wang W, Tu Z. Aberrantly DNA methylated-differentially expressed genes and pathways in hepatocellular carcinoma. J Cancer, 2019, 10(2): 355-366.
22.	Yang X, Miao BS, Wei CY, et al. Lymphoid-specific helicase promotes the growth and invasion of hepatocellular carcinoma by transcriptional regulation of centromere protein F expression. Cancer Sci, 2019, 110(7): 2133-2144.
23.	Dai Y, Liu L, Zeng T, et al. Characterization of the oncogenic function of centromere protein F in hepatocellular carcinoma. Biochem Biophys Res Commun, 2013, 436(4): 711-718.
24.	Peterka M, Kornmann B. Miro-dependent mitochondrial pool of CENP-F and its farnesylated C-terminal domain are dispensable for normal development in mice. PloS Genet, 2019, 15(3): e1008050.

1. Barta JA, Powell CA, Wisnivesky JP. Global epidemiology of lung cancer. Ann Glob Health, 2019, 85(1): 8.
2. Zhang XC, Wang J, Shao GG, et al. Comprehensive genomic and immunological characterization of Chinese non-small cell lung cancer patients. Nat Commun, 2019, 10(1): 1772.
3. Duan Y, Liu G, Sun Y, et al. COL6A3 polymorphisms were associated with lung cancer risk in a Chinese population. Respir Res, 2019, 20(1): 143.
4. Hsieh CP, Hsieh MJ, Wu CF, et al. Prognostic factors in non-small cell lung cancer patients who received neoadjuvant therapy and curative resection. J Thorac Dis, 2016, 8(7): 1477-1486.
5. Rattner JB, Rao A, Fritzler MJ, et al. CENP-F is a.ca 400 kDa kinetochore protein that exhibits a cell-cycle dependent localization. Cell Motil Cytoskeleton, 1993, 26(3): 214-226.
6. Sang M, Wu M, Meng L, et al. Identification of epithelial-mesenchymal transition-related circRNA-miRNA-mRNA ceRNA regulatory network in breast cancer. Pathol Res Pract, 2020, 216(9): 153088.
7. An F, Zhang Z, Xia M. Functional analysis of the nasopharyngeal carcinoma primary tumorassociated gene interaction network. Mol Med Rep, 2015, 12(4): 4975-4980.
8. Koon N, Schneider-Stock R, Sarlomo-Rikala M, et al. Molecular targets for tumour progression in gastrointestinal stromal tumours. Gut, 2004, 53(2): 235-240.
9. Li R, Wang X, Zhao X, et al. Centromere protein F and Forkhead box M1 correlation with prognosis of non-small cell lung cancer. Oncol Lett, 2020, 19(2): 1368-1374.
10. Sun CC, Li SJ, Hu W, et al. Comprehensive analysis of the expression and prognosis for E2Fs in human breast cancer. Mol Ther, 2019, 27(6): 1153-1165.
11. Yang X, Zhu S, Li L, et al. Identification of differentially expressed genes and signaling pathways in ovarian cancer by integrated bioinformatics analysis. Onco Targets Ther, 2018, 11: 1457-1474.
12. Shang S, Wang L, Su Y, et al. Local therapy combined with chemotherapy versus chemotherapy for postoperative oligometastatic non-small-cell lung cancer. Future Oncol, 2019, 15(14): 1593-1603.
13. Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature, 2018, 553(7689): 446-454.
14. Ko EC, Raben D, Formenti SC. The integration of radiotherapy with immunotherapy for the treatment of non-small cell lung cancer. Clin Cancer Res, 2018, 24(23): 5792-5806.
15. 宁晔, 谢冬, 佘云浪, 等. 2020版NCCN肺癌筛查指南解读. 中国胸心血管外科临床杂志, 2020, 27(3): 251-254.
16. Wu SG, Shih JY. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer, 2018, 17(1): 38.
17. Yu B, Chen L, Zhang W, et al. TOP2A and CENPF are synergistic master regulators activated in cervical cancer. BMC Med Genomics, 2020, 13(1): 145.
18. Sun J, Huang J, Lan J, et al. Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer. Cancer Cell Int, 2019, 19: 264.
19. Aytes A, Mitrofanova A, Lefebvre C, et al. Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy. Cancer Cell, 2014, 25(5): 638-651.
20. Shahid M, Lee MY, Piplani H, et al. Centromere protein F (CENPF), a microtubule binding protein, modulates cancer metabolism by regulating pyruvate kinase M2 phosphorylation signaling. Cell Cycle, 2018, 17(24): 2802-2818.
21. Cai C, Wang W, Tu Z. Aberrantly DNA methylated-differentially expressed genes and pathways in hepatocellular carcinoma. J Cancer, 2019, 10(2): 355-366.
22. Yang X, Miao BS, Wei CY, et al. Lymphoid-specific helicase promotes the growth and invasion of hepatocellular carcinoma by transcriptional regulation of centromere protein F expression. Cancer Sci, 2019, 110(7): 2133-2144.
23. Dai Y, Liu L, Zeng T, et al. Characterization of the oncogenic function of centromere protein F in hepatocellular carcinoma. Biochem Biophys Res Commun, 2013, 436(4): 711-718.
24. Peterka M, Kornmann B. Miro-dependent mitochondrial pool of CENP-F and its farnesylated C-terminal domain are dispensable for normal development in mice. PloS Genet, 2019, 15(3): e1008050.

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Effects of centromere protein F expression on biological behavior and prognosis of non-small cell lung cancer

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