The bioinformatics analysis of hub genes in hepatocellular carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HUANG Kang ,  PENG Guizhu

Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan 430071, P. R. China;

Corresponding author：

PENG Guizhu, Email: pengguizhu@139.com

Keywords：

hepatocellular carcinoma; hub gene; bioinformatics analysis

DOI：

10.7507/1007-9424.202002087

Video：

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Objective To screen differential expression of genes in hepatocellular carcinoma (HCC) by bioinformatics method, and analyze its clinical significance and its possible molecular mechanism in HCC.Methods The HCC gene expression profile GSE101728 was picked out to analyze the differential expression genes. The hub genes were identified by STRING and Cytoscape. GO and KEGG analysis were carried out by using DAVID and PPI network were constructed by STRING. The relationship among the hub genes were analyzed by using GEPIA.Results A total of 1 082 DEGs were captured (354 up-regulated genes and 728 down-regulated genes). Meantime, 10 hub genes ［cyclin dependent kinase 1 (CDK1), cyclin B1 (CCNB1), cyclin A2 (CCNA2), polo-like kinase 1 (PLK1), laser kinase B (AURKB), cyclin of cell division 20 (CDC20), centromere protein A (CENPA), mitotic arrest defective protein 2 (MAD2L1), cyclin B2 (CCNB2), and kinesin family 2C (KIF2C)］ were identified, and its expression and clinical significance were verified by GEPIA. GO and KEGG analysis showed 10 hub genes were mainly enriched in cell division and cell cycle. Expressions of AURKB, CCNB1, and MAD2L1 were obviously positively correlated (P<0.05).Conclusion This study analyzes the hub genes in the development of HCC by bioinformatics methods and provides valuable information for further research on the mechanism of HCC.

Citation： HUANG Kang, PENG Guizhu. The bioinformatics analysis of hub genes in hepatocellular carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(11): 1357-1364. doi: 10.7507/1007-9424.202002087 Copy

1.	陈万青, 崔富强, 樊春笋, 等. 中国肝癌一级预防专家共识 (2018). 中国肿瘤, 2018, 27(9): 660-669.
2.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin, 2017, 67(1): 7-30.
3.	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.
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5.	Kudo M. Systemic therapy for hepatocellular carcinoma: 2017 update. Oncology, 2017, 93(Suppl 1): 135-146.
6.	Zhu HR, Yu XN, Zhang GC, et al. Comprehensive analysis of long non-coding RNA-messenger RNA-microRNA co-expression network identifies cell cycle-related lncRNA in hepatocellular carcinoma. Int J Mol Med, 2019, 44(5): 1844-1854.
7.	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.
8.	McIntosh JR. Mitosis. Cold Spring Harb Perspect Biol, 2016, 8(9): a023218.
9.	Otto T, Sicinski P. Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer, 2017, 17(2): 93-115.
10.	Zheng K, He Z, Kitazato K, et al. Selective autophagy regulates cell cycle in cancer therapy. Theranostics, 2019, 9(1): 104-125.
11.	Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer, 2009, 9(3): 153-166.
12.	Zhou J, Han S, Qian W, et al. Metformin induces miR-378 to downregulate the CDK1, leading to suppression of cell proliferation in hepatocellular carcinoma. Onco Targets Ther, 2018, 11: 4451-4459.
13.	Tibes R, McDonagh KT, Lekakis L, et al. Phase Ⅰ study of the novel Cdc2/CDK1 and AKT inhibitor terameprocol in patients with advanced leukemias. Invest New Drugs, 2015, 33(2): 389-396.
14.	Takashima S, Saito H, Takahashi N, et al. Strong expression of cyclin B2 mRNA correlates with a poor prognosis in patients with non-small cell lung cancer. Tumour Biol, 2014, 35(5): 4257-4265.
15.	Jackman M, Firth M, Pines J. Human cyclins B1 and B2 are localized to strikingly different structures: B1 to microtubules, B2 primarily to the Golgi apparatus. EMBO J, 1995, 14(8): 1646-1654.
16.	Fang Y, Yu H, Liang X, et al. Chk1-induced CCNB1 overex-pression promotes cell proliferation and tumor growth in human colorectal cancer. Cancer Biol Ther, 2014, 15(9): 1268-1279.
17.	Bie L, Zhao G, Ju Y, et al. Integrative genomic analysis identifies CCNB1 and CDC2 as candidate genes associated with meningioma recurrence. Cancer Genet, 2011, 204(10): 536-540.
18.	Cheung CT, Bendris N, Paul C, et al. Cyclin A2 modulates EMT via β-catenin and phospholipase C pathways. Carcinogenesis, 2015, 36(8): 914-924.
19.	Donaldson MM, Tavares AA, Hagan IM, et al. The mitotic roles of polo-like kinase. J Cell Sci, 2001, 114(Pt 13): 2357-2358.
20.	Lansing TJ, McConnell RT, Duckett DR, et al. In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1. Mol Cancer Ther, 2007, 6(2): 450-459.
21.	Weiss GJ, Jameson G, Von Hoff DD, et al. Phase Ⅰ dose escalation study of NMS-1286937, an orally available polo-like kinase 1 inhibitor, in patients with advanced or metastatic solid tumors. Invest New Drugs, 2018, 36(1): 85-95.
22.	Yan M, Wang C, He B, et al. Aurora-a kinase: a potent oncogene and target for cancer therapy. Med Res Rev, 2016, 36(6): 1036-1079.
23.	Lin ZZ, Jeng YM, Hu FC, et al. Significance of aurora B overexpression in hepatocellular carcinoma. Aurora B overexpression in HCC. BMC Cancer, 2010, 10: 461.
24.	Lens SM, Voest EE, Medema RH. Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer, 2010, 10(12): 825-841.
25.	Schwartz GK, Carvajal RD, Midgley R, et al. Phase Ⅰ Study of Barasertib (AZD1152), a selective inhibitor of aurora b kinase, in patients with advanced solid tumors. Invest New Drugs, 2013, 31(2): 370-380.
26.	Primorac I, Musacchio A. Panta rhei: the APC/C at steady state. J Cell Biol, 2013, 201(2): 177-189.
27.	Gayyed MF, El-Maqsoud NM, Tawfiek ER, et al. A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: its correlation with tumor grade and stage. Tumour Biol, 2016, 37(1): 749-762.
28.	Li Y, Bai W, Zhang J. MiR-200c-5p suppresses proliferation and metastasis of human hepatocellular carcinoma (HCC) via suppressing MAD2L1. Biomed Pharmacother, 2017, 92: 1038-1044.
29.	Zaganjor E, Osborne JK, Weil LM, et al. Ras regulates kinesin 13 family members to control cell migration pathways in transformed human bronchial epithelial cells. Oncogene, 2014, 33(47): 5457-5466.
30.	Chen J, Li S, Zhou S, et al. Kinesin superfamily protein expression and its association with progression and prognosis in hepatocellular carcinoma. J Cancer Res Ther, 2017, 13(4): 651-659.
31.	Valdivia MM, Hamdouch K, Ortiz M, et al. CENPA a genomic marker for centromere activity and human diseases. Curr Genomics, 2009, 10(5): 326-335.
32.	Takada M, Zhang W, Suzuki A, et al. FBW7 loss promotes chromosomal instability and tumorigenesis via cyclin E1/CDK2-mediated phosphorylation of CENP-A. Cancer Res, 2017, 77(18): 4881-4893.

1. 陈万青, 崔富强, 樊春笋, 等. 中国肝癌一级预防专家共识 (2018). 中国肿瘤, 2018, 27(9): 660-669.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin, 2017, 67(1): 7-30.
3. 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.
4. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
5. Kudo M. Systemic therapy for hepatocellular carcinoma: 2017 update. Oncology, 2017, 93(Suppl 1): 135-146.
6. Zhu HR, Yu XN, Zhang GC, et al. Comprehensive analysis of long non-coding RNA-messenger RNA-microRNA co-expression network identifies cell cycle-related lncRNA in hepatocellular carcinoma. Int J Mol Med, 2019, 44(5): 1844-1854.
7. 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.
8. McIntosh JR. Mitosis. Cold Spring Harb Perspect Biol, 2016, 8(9): a023218.
9. Otto T, Sicinski P. Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer, 2017, 17(2): 93-115.
10. Zheng K, He Z, Kitazato K, et al. Selective autophagy regulates cell cycle in cancer therapy. Theranostics, 2019, 9(1): 104-125.
11. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer, 2009, 9(3): 153-166.
12. Zhou J, Han S, Qian W, et al. Metformin induces miR-378 to downregulate the CDK1, leading to suppression of cell proliferation in hepatocellular carcinoma. Onco Targets Ther, 2018, 11: 4451-4459.
13. Tibes R, McDonagh KT, Lekakis L, et al. Phase Ⅰ study of the novel Cdc2/CDK1 and AKT inhibitor terameprocol in patients with advanced leukemias. Invest New Drugs, 2015, 33(2): 389-396.
14. Takashima S, Saito H, Takahashi N, et al. Strong expression of cyclin B2 mRNA correlates with a poor prognosis in patients with non-small cell lung cancer. Tumour Biol, 2014, 35(5): 4257-4265.
15. Jackman M, Firth M, Pines J. Human cyclins B1 and B2 are localized to strikingly different structures: B1 to microtubules, B2 primarily to the Golgi apparatus. EMBO J, 1995, 14(8): 1646-1654.
16. Fang Y, Yu H, Liang X, et al. Chk1-induced CCNB1 overex-pression promotes cell proliferation and tumor growth in human colorectal cancer. Cancer Biol Ther, 2014, 15(9): 1268-1279.
17. Bie L, Zhao G, Ju Y, et al. Integrative genomic analysis identifies CCNB1 and CDC2 as candidate genes associated with meningioma recurrence. Cancer Genet, 2011, 204(10): 536-540.
18. Cheung CT, Bendris N, Paul C, et al. Cyclin A2 modulates EMT via β-catenin and phospholipase C pathways. Carcinogenesis, 2015, 36(8): 914-924.
19. Donaldson MM, Tavares AA, Hagan IM, et al. The mitotic roles of polo-like kinase. J Cell Sci, 2001, 114(Pt 13): 2357-2358.
20. Lansing TJ, McConnell RT, Duckett DR, et al. In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1. Mol Cancer Ther, 2007, 6(2): 450-459.
21. Weiss GJ, Jameson G, Von Hoff DD, et al. Phase Ⅰ dose escalation study of NMS-1286937, an orally available polo-like kinase 1 inhibitor, in patients with advanced or metastatic solid tumors. Invest New Drugs, 2018, 36(1): 85-95.
22. Yan M, Wang C, He B, et al. Aurora-a kinase: a potent oncogene and target for cancer therapy. Med Res Rev, 2016, 36(6): 1036-1079.
23. Lin ZZ, Jeng YM, Hu FC, et al. Significance of aurora B overexpression in hepatocellular carcinoma. Aurora B overexpression in HCC. BMC Cancer, 2010, 10: 461.
24. Lens SM, Voest EE, Medema RH. Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer, 2010, 10(12): 825-841.
25. Schwartz GK, Carvajal RD, Midgley R, et al. Phase Ⅰ Study of Barasertib (AZD1152), a selective inhibitor of aurora b kinase, in patients with advanced solid tumors. Invest New Drugs, 2013, 31(2): 370-380.
26. Primorac I, Musacchio A. Panta rhei: the APC/C at steady state. J Cell Biol, 2013, 201(2): 177-189.
27. Gayyed MF, El-Maqsoud NM, Tawfiek ER, et al. A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: its correlation with tumor grade and stage. Tumour Biol, 2016, 37(1): 749-762.
28. Li Y, Bai W, Zhang J. MiR-200c-5p suppresses proliferation and metastasis of human hepatocellular carcinoma (HCC) via suppressing MAD2L1. Biomed Pharmacother, 2017, 92: 1038-1044.
29. Zaganjor E, Osborne JK, Weil LM, et al. Ras regulates kinesin 13 family members to control cell migration pathways in transformed human bronchial epithelial cells. Oncogene, 2014, 33(47): 5457-5466.
30. Chen J, Li S, Zhou S, et al. Kinesin superfamily protein expression and its association with progression and prognosis in hepatocellular carcinoma. J Cancer Res Ther, 2017, 13(4): 651-659.
31. Valdivia MM, Hamdouch K, Ortiz M, et al. CENPA a genomic marker for centromere activity and human diseases. Curr Genomics, 2009, 10(5): 326-335.
32. Takada M, Zhang W, Suzuki A, et al. FBW7 loss promotes chromosomal instability and tumorigenesis via cyclin E1/CDK2-mediated phosphorylation of CENP-A. Cancer Res, 2017, 77(18): 4881-4893.

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