Lung cancer (LC), which includes small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), is common and has a high fatality rate. This study aimed to reveal the prognostic mechanisms of LC. GSE30219 was extracted from the Gene Expression Omnibus (GEO) database, and included 293 LC samples and 14 normal lung samples. Differentially expressed genes (DEGs) were identified using the Limma package, and subjected to pathway enrichment analysis using DAVID. MicroRNAs (miRNAs) targeting the DEGs were predicted using Webgestalt. Cytoscape software was used to build a protein-protein interaction (PPI) network and to identify significant network modules. Survival analysis was conducted using Survminer and Survival packages, and validation was performed using The Cancer Genome Atlas (TCGA) dataset. The good and poor prognosis groups contained 518 DEGs. miR-190, miR-493, and miR-218 for the upregulated genes and miR-302, miR-200, and miR-26 for the downregulated genes were predicted. Three network modules (module 1, 2, and 3) were identified from the PPI network. CDK1, MCM10, and NDC80 were the core nodes of module 1, 2, and 3, respectively. In module 1, CDK1 interacted with both CCNB1 and CCNB2. Additionally, CDK1, CCNB1, CCNB2, MCM10, and NDC80 expression levels correlated with clinical survival and were identified as DEGs in both GSE30219 and the TCGA dataset. miR-190, miR-493, miR-218, miR-200, and miR-302 might act in LC by targeting the DEGs. CDK1, CCNB1, CCNB2, MCM10, and NDC80 might also influence the prognosis of LC.
2. Collins LG, Haines C, Perkel R, Enck RE. Lung cancer: diagnosis and management. Am Fam Physician. 2007;75(1):56-63.
3. Mcguire S. World Cancer Report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Adv Nutr. 2016;7(2):418. DOI: 10.3945/an.116.012211
4. Tan X, Fang Z, Wan J, Jie H, Chen Z, Li B et al. Pin1 expression contributes to lung cancer prognosis and carcinogenesis. Cancer Biol Ther. 2010;9(2):111-9. DOI: 10.4161/cbt.9.2.10341
5. Yoon HE, Kim SA, Choi HS, Ahn MY, Yoon JH, Ahn SG. Inhibition of Plk1 and Pin1 by 5′-nitro-indirubinoxime suppresses human lung cancer cells. Cancer Lett. 2012;316(1):97-104. DOI: 10.1016/j.canlet.2011.10.029
6. Dong QZ, Wang Y, Dong XJ, Li ZX, Tang ZP, Cui QZ et al. CIP2A is Overexpressed in Non-Small Cell Lung Cancer and Correlates with Poor Prognosis. Ann Surg Oncol. 2011;18(3):857. DOI: 10.1245/s10434-010-1313-8
7. Xu P, Xu XL, Huang Q, Zhang ZH, Zhang YB. CIP2A with survivin protein expressions in human non-small. Med Oncol. 2012;29(3):1643-7. DOI: 10.1007/s12032-011-0053-3
8. Ni S, Xu L, Huang J, Feng J, Zhu H, Wang G et al. Increased ZO-1 expression predicts valuable prognosis in non-small cell lung cancer. Int J Clin Exp Pathol. 2013;6(12):2887-95.
9. Gao W, Yu Y, Cao H, Shen H, Li X, Pan S et al. Deregulated expression of miR-21, miR-143 and miR-181a in non small cell lung cancer is related to clinicopathologic characteristics or patient prognosis. Biomed Pharmacother. 2010;64(6):399. DOI: 10.1016/j.biopha.2010.01.018
10. Rousseaux S, Debernardi A, Jacquiau B, Vitte AL, Vesin A, Nagymignotte H et al. Ectopic Activation of Germline and Placental Genes Identifies Aggressive Metastasis-Prone Lung Cancers. Sci Transl Med. 2013;5(186):186ra66. DOI: 10.1126/scitranslmed.3005723
11. Irizarry RA, Wu Z, Jaffee HA. Comparison of Affymetrix GeneChip expression measures. Bioinformatics. 2006;22(7):789. DOI: 10.1093/bioinformatics/btk046
12. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7). DOI: 10.1093/nar/gkv007
13. Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44. DOI: 10.1038/nprot.2008.211
14. Kanehisa M, Sato Y, Kawashima M, Furumichi M, Tanabe M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 2015;44(D1):D457-D62. DOI: 10.1093/nar/gkv1070
15. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522-31. DOI: 10.1038/nrg1379
16. Wang J, Duncan D, Shi Z, Zhang B. WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res. 2013;41(W1):77-83. DOI: 10.1093/nar/gkt439
17. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A et al. STRING v9. 1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2013;41(D1):D808-D15. DOI: 10.1093/nar/gks1094
18. Saito R, Smoot ME, Ono K, Ruscheinski J, Wang P-L, Lotia S et al. A travel guide to Cytoscape plugins. Nat Methods. 2012;9(11):1069-76. DOI: 10.1038/nmeth.2212
19. Morris JH, Apeltsin L, Newman AM, Baumbach J, Wittkop T, Su G et al. clusterMaker: a multi-algorithm clustering plugin for Cytoscape. BMC bioinformatics. 2011;12:436 DOI: 10.1186/1471-2105-12-436. DOI: 10.1186/1471-2105-12-436
21. Maere S, Heymans K, Kuiper M. BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics. 2005 Aug 15;21(16):3448-9 DOI: 10.1093/bioinformatics/bti551. DOI: 10.1093/bioinformatics/bti551
26. Jia WZ, Tao Y, Qi A, Hua Y, Zhu Z, Xiao L et al. MicroRNA-190 regulatesFOXP2genes in human gastric cancer. Onco Targets Ther. 2016;9(Issue 1):3643-51.
27. Yu Y, Luo W, Yang ZJ, Chi JR, Li YR, Ding Y et al. miR-190 suppresses breast cancer metastasis by regulation of TGF-Î²-induced epithelial-mesenchymal transition. Mol Cancer. 2018;17(1):70. DOI: 10.1186/s12943-018-0818-9
28. Liang Z, Kong R, He Z, Lin LY, Qin SS, Chen CY et al. High expression of miR-493-5p positively correlates with clinical prognosis of non small cell lung cancer by targeting oncogene ITGB1. Oncotarget. 2017;8(29):47389-99. DOI: 10.18632/oncotarget.17650
29. Peng Z, Pan L, Niu Z, Li W, Dang X, Lin W et al. Identification of microRNAs as potential biomarkers for lung adenocarcinoma using integrating genomics analysis. Oncotarget. 2017;8(38):64143. DOI: 10.18632/oncotarget.19358
30. Si L, Tian H, Yue W, Li L, Li S, Gao C et al. Potential use of microRNA-200c as a prognostic marker in non-small cell lung cancer. Oncol Lett. 2017;14(4):4325. DOI: 10.3892/ol.2017.6667
31. Li J, Yu J, Zhang H, Wang B, Guo H, Bai J et al. Exosomes-Derived MiR-302b Suppresses Lung Cancer Cell Proliferation and Migration via TGF beta RII Inhibition. Cell Physiol Biochem. 2016;38(5):1715. DOI: 10.1159/000443111
32. Shi YX, Zhu T, Zou T, Zhuo W, Chen YX, Huang MS et al. Prognostic and predictive values of CDK1 and MAD2L1 in lung adenocarcinoma. Oncotarget. 2016;7(51):85235. DOI: 10.18632/oncotarget.13252
33. Huang SH, Xiao-Li MA, Qiu C, Huang JA, Kong WH, Xie JW et al. The overexpression of cyclin B1 and CDK1 in lung carcinoma and its clinical significance. Journal of Shandong University. 2004;39(5):122-4.
34. Jacquot C, Rousseau B, Carbonnelle D, Chinou I, Malleter M, Tomasoni C et al. Cucurbitacin-D-induced CDK1 mRNA up-regulation causes proliferation arrest of a non-small cell lung carcinoma cell line (NSCLC-N6). Anticancer Res. 2014;34(9):4797-806.
35. Cooper WA, Kohonencorish MR, Mccaughan B, Kennedy C, Sutherland RL, Lee CS. Expression and prognostic significance of cyclin B1 and cyclin A in non-small cell lung cancer. Histopathology. 2009;55(1):28-36. DOI: 10.1111/j.1365-2559.2009.03331.x
36. Takashima S, Saito H, Takahashi N, Imai K, Kudo S, Atari M 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):4257-65. DOI: 10.1007/s13277-013-1556-7
37. Liu YZ, Wang BS, Jiang YY, Cao J, Hao JJ, Zhang Y et al. MCMs expression in lung cancer: implication of prognostic significance. J Cancer. 2017;8(18):3641-7. DOI: 10.7150/jca.20777
38. Liu YZ, Jiang YY, Hao JJ, Lu SS, Zhang TT, Shang L et al. Prognostic significance of MCM7 expression in the bronchial brushings of patients with non-small cell lung cancer (NSCLC). Lung Cancer. 2012;77(1):176. DOI: 10.1016/j.lungcan.2012.03.001
39. Kikuchia J, Kinoshitab I, Shimizub Y, Kikuchia E, Takedab K, Abu H. Minichromosome maintenance (MCM) protein 4 as a marker for proliferation and its clinical and clinicopathological significance in non-small cell lung cancer. Lung Cancer. 2011;72(2):229-37. DOI: 10.1016/j.lungcan.2010.08.020
40. Chao W. Integrating gene expression and protein-protein interaction network to prioritize cancer-associated genes. BMC bioinformatics. 2012;13(1):182. DOI: 10.1186/1471-2105-13-182
41. Hayama S, Daigo Y, Kato T, Ishikawa N, Yamabuki T, Miyamoto M et al. Activation of CDCA1-KNTC2, Members of Centromere Protein Complex, Involved in Pulmonary Carcinogenesis. 2006;66(21):10339-48.