Iranian Red Crescent Medical Journal

Published by: Kowsar

Identification of CDKN3 and UBE2C mRNAs as Prognostic Biomarkers in Early-Stage Lung Adenocarcinoma Using Bioinformatics Strategy

Qiang Chen 1 , 2 , 3 , * , Lutong Xu 1 , Jing Hu 1 , 2 , 3 , Tonglian Wang 1 , Kang Zhang 1 , Hongbo Zhao 4 , Yuanyue Li 1 and Tao Shou 2 , 3
Authors Information
1 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China
2 Medical Oncology, The First People’s Hospital of Yunnan Province, Kunming, China
3 Medical Oncology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
4 Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, China
Article information
  • Iranian Red Crescent Medical Journal: March 31, 2019, 21 (3); e86174
  • Published Online: March 5, 2019
  • Article Type: Research Article
  • Received: November 8, 2018
  • Revised: February 13, 2019
  • Accepted: February 17, 2019
  • DOI: 10.5812/ircmj.86174

To Cite: Chen Q, Xu L, Hu J, Wang T, Zhang K, et al. Identification of CDKN3 and UBE2C mRNAs as Prognostic Biomarkers in Early-Stage Lung Adenocarcinoma Using Bioinformatics Strategy, Iran Red Crescent Med J. 2019 ; 21(3):e86174. doi: 10.5812/ircmj.86174.

Copyright © 2019, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited
1. Background
2. Objectives
3. Methods
4. Results
5. Discussion
  • 1. Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Adv Exp Med Biol. 2016;893:1-19. doi: 10.1007/978-3-319-24223-1_1. [PubMed: 26667336].
  • 2. Blandin Knight S, Crosbie PA, Balata H, Chudziak J, Hussell T, Dive C. Progress and prospects of early detection in lung cancer. Open Biol. 2017;7(9). doi: 10.1098/rsob.170070. [PubMed: 28878044]. [PubMed Central: PMC5627048].
  • 3. Walters S, Maringe C, Coleman MP, Peake MD, Butler J, Young N, et al. Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: A population-based study, 2004-2007. Thorax. 2013;68(6):551-64. doi: 10.1136/thoraxjnl-2012-202297. [PubMed: 23399908].
  • 4. Wu K, House L, Liu W, Cho WC. Personalized targeted therapy for lung cancer. Int J Mol Sci. 2012;13(9):11471-96. doi: 10.3390/ijms130911471. [PubMed: 23109866]. [PubMed Central: PMC3472758].
  • 5. Krzystanek M, Moldvay J, Szuts D, Szallasi Z, Eklund AC. A robust prognostic gene expression signature for early stage lung adenocarcinoma. Biomark Res. 2016;4:4. doi: 10.1186/s40364-016-0058-3. [PubMed: 26900477]. [PubMed Central: PMC4761211].
  • 6. Nesbitt JC, Putnam JB Jr, Walsh GL, Roth JA, Mountain CF. Survival in early-stage non-small cell lung cancer. Ann Thorac Surg. 1995;60(2):466-72. [PubMed: 7646126].
  • 7. Saito M, Shiraishi K, Kunitoh H, Takenoshita S, Yokota J, Kohno T. Gene aberrations for precision medicine against lung adenocarcinoma. Cancer Sci. 2016;107(6):713-20. doi: 10.1111/cas.12941. [PubMed: 27027665]. [PubMed Central: PMC4968599].
  • 8. Zhao J, Li L, Wang Q, Han H, Zhan Q, Xu M. CircRNA expression profile in early-stage lung adenocarcinoma patients. Cell Physiol Biochem. 2017;44(6):2138-46. doi: 10.1159/000485953. [PubMed: 29241190].
  • 9. Pasche B, Grant SC. Non-small cell lung cancer and precision medicine: A model for the incorporation of genomic features into clinical trial design. JAMA. 2014;311(19):1975-6. doi: 10.1001/jama.2014.3742. [PubMed: 24846033].
  • 10. He X, Zhang C, Shi C, Lu Q. 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):929-38. doi: 10.3892/or.2018.6197. [PubMed: 29328493].
  • 11. Landi MT, Dracheva T, Rotunno M, Figueroa JD, Liu H, Dasgupta A, et al. Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival. PLoS One. 2008;3(2). e1651. doi: 10.1371/journal.pone.0001651. [PubMed: 18297132]. [PubMed Central: PMC2249927].
  • 12. Lu TP, Tsai MH, Lee JM, Hsu CP, Chen PC, Lin CW, et al. Identification of a novel biomarker, SEMA5A, for non-small cell lung carcinoma in nonsmoking women. Cancer Epidemiol Biomarkers Prev. 2010;19(10):2590-7. doi: 10.1158/1055-9965.EPI-10-0332. [PubMed: 20802022].
  • 13. Caliez J, Monnet I, Pujals A, Rousseau-Bussac G, Jabot L, Boudjemaa A, et al. [Lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement]. Rev Mal Respir. 2017;34(5):576-80. French. doi: 10.1016/j.rmr.2016.08.002. [PubMed: 27646667].
  • 14. Gautier L, Cope L, Bolstad BM, Irizarry RA. affy--analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004;20(3):307-15. doi: 10.1093/bioinformatics/btg405. [PubMed: 14960456].
  • 15. 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). e47. doi: 10.1093/nar/gkv007. [PubMed: 25605792]. [PubMed Central: PMC4402510].
  • 16. Yu G, Wang LG, Han Y, He QY. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS. 2012;16(5):284-7. doi: 10.1089/omi.2011.0118. [PubMed: 22455463]. [PubMed Central: PMC3339379].
  • 17. Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, et al. STRING v10: Protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43(Database issue):D447-52. doi: 10.1093/nar/gku1003. [PubMed: 25352553]. [PubMed Central: PMC4383874].
  • 18. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498-504. doi: 10.1101/gr.1239303. [PubMed: 14597658]. [PubMed Central: PMC403769].
  • 19. Bader GD, Hogue CW. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics. 2003;4:2. [PubMed: 12525261]. [PubMed Central: PMC149346].
  • 20. Tang Y, Li M, Wang J, Pan Y, Wu FX. CytoNCA: A cytoscape plugin for centrality analysis and evaluation of protein interaction networks. Biosystems. 2015;127:67-72. doi: 10.1016/j.biosystems.2014.11.005. [PubMed: 25451770].
  • 21. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98-W102. doi: 10.1093/nar/gkx247. [PubMed: 28407145]. [PubMed Central: PMC5570223].
  • 22. Cress WD, Yu P, Wu J. Expression and alternative splicing of the cyclin-dependent kinase inhibitor-3 gene in human cancer. Int J Biochem Cell Biol. 2017;91(Pt B):98-101. doi: 10.1016/j.biocel.2017.05.013. [PubMed: 28504190]. [PubMed Central: PMC5641230].
  • 23. Nalepa G, Barnholtz-Sloan J, Enzor R, Dey D, He Y, Gehlhausen JR, et al. The tumor suppressor CDKN3 controls mitosis. J Cell Biol. 2013;201(7):997-1012. doi: 10.1083/jcb.201205125. [PubMed: 23775190]. [PubMed Central: PMC3691455].
  • 24. Yu C, Cao H, He X, Sun P, Feng Y, Chen L, et al. Cyclin-dependent kinase inhibitor 3 (CDKN3) plays a critical role in prostate cancer via regulating cell cycle and DNA replication signaling. Biomed Pharmacother. 2017;96:1109-18. doi: 10.1016/j.biopha.2017.11.112. [PubMed: 29196103].
  • 25. Zhang LP, Li WJ, Zhu YF, Huang SY, Fang SY, Shen L, et al. CDKN3 knockdown reduces cell proliferation, invasion and promotes apoptosis in human ovarian cancer. Int J Clin Exp Pathol. 2015;8(5):4535-44. [PubMed: 26191143]. [PubMed Central: PMC4503015].
  • 26. Barron EV, Roman-Bassaure E, Sanchez-Sandoval AL, Espinosa AM, Guardado-Estrada M, Medina I, et al. CDKN3 mRNA as a biomarker for survival and therapeutic target in cervical cancer. PLoS One. 2015;10(9). e0137397. doi: 10.1371/journal.pone.0137397. [PubMed: 26372210]. [PubMed Central: PMC4570808].
  • 27. Yang C, Sun JJ. Mechanistic studies of cyclin-dependent kinase inhibitor 3 (CDKN3) in colorectal cancer. Asian Pac J Cancer Prev. 2015;16(3):965-70. [PubMed: 25735390].
  • 28. Li Y, Ji S, Fu LY, Jiang T, Wu D, Meng FD. Knockdown of cyclin-dependent kinase inhibitor 3 inhibits proliferation and invasion in human gastric cancer cells. Oncol Res. 2017;25(5):721-31. doi: 10.3727/096504016X14772375848616. [PubMed: 27983933].
  • 29. Deng M, Wang J, Chen Y, Zhang L, Xie G, Liu Q, et al. Silencing cyclin-dependent kinase inhibitor 3 inhibits the migration of breast cancer cell lines. Mol Med Rep. 2016;14(2):1523-30. doi: 10.3892/mmr.2016.5401. [PubMed: 27314680]. [PubMed Central: PMC4940103].
  • 30. Fan C, Chen L, Huang Q, Shen T, Welsh EA, Teer JK, et al. Overexpression of major CDKN3 transcripts is associated with poor survival in lung adenocarcinoma. Br J Cancer. 2015;113(12):1735-43. doi: 10.1038/bjc.2015.378. [PubMed: 26554648]. [PubMed Central: PMC4701993].
  • 31. Hao Z, Zhang H, Cowell J. Ubiquitin-conjugating enzyme UBE2C: Molecular biology, role in tumorigenesis, and potential as a biomarker. Tumour Biol. 2012;33(3):723-30. doi: 10.1007/s13277-011-0291-1. [PubMed: 22170434].
  • 32. Loussouarn D, Campion L, Leclair F, Campone M, Charbonnel C, Ricolleau G, et al. Validation of UBE2C protein as a prognostic marker in node-positive breast cancer. Br J Cancer. 2009;101(1):166-73. doi: 10.1038/sj.bjc.6605122. [PubMed: 19513072]. [PubMed Central: PMC2713693].
  • 33. Zhang HQ, Zhao G, Ke B, Ma G, Liu GL, Liang H, et al. Overexpression of UBE2C correlates with poor prognosis in gastric cancer patients. Eur Rev Med Pharmacol Sci. 2018;22(6):1665-71. doi: 10.26355/eurrev_201803_14578. [PubMed: 29630110].
  • 34. Zhang J, Liu X, Yu G, Liu L, Wang J, Chen X, et al. UBE2C is a potential biomarker of intestinal-type gastric cancer with chromosomal instability. Front Pharmacol. 2018;9:847. doi: 10.3389/fphar.2018.00847. [PubMed: 30116193]. [PubMed Central: PMC6082955].
  • 35. Psyrri A, Kalogeras KT, Kronenwett R, Wirtz RM, Batistatou A, Bournakis E, et al. Prognostic significance of UBE2C mRNA expression in high-risk early breast cancer. A hellenic cooperative oncology group (HeCOG) study. Ann Oncol. 2012;23(6):1422-7. doi: 10.1093/annonc/mdr527. [PubMed: 22056852].
  • 36. Ma R, Kang X, Zhang G, Fang F, Du Y, Lv H. High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma. Oncol Lett. 2016;11(3):2300-4. doi: 10.3892/ol.2016.4171. [PubMed: 26998166]. [PubMed Central: PMC4774622].
  • 37. Morikawa T, Kawai T, Abe H, Kume H, Homma Y, Fukayama M. UBE2C is a marker of unfavorable prognosis in bladder cancer after radical cystectomy. Int J Clin Exp Pathol. 2013;6(7):1367-74. [PubMed: 23826418]. [PubMed Central: PMC3693202].
  • 38. Guo J, Wu Y, Du J, Yang L, Chen W, Gong K, et al. Deregulation of UBE2C-mediated autophagy repression aggravates NSCLC progression. Oncogenesis. 2018;7(6):49. doi: 10.1038/s41389-018-0054-6. [PubMed: 29904125]. [PubMed Central: PMC6002383].
  • 39. Liu S, Yang TB, Nan YL, Li AH, Pan DX, Xu Y, et al. Genetic variants of cell cycle pathway genes predict disease-free survival of hepatocellular carcinoma. Cancer Med. 2017;6(7):1512-22. doi: 10.1002/cam4.1067. [PubMed: 28639733]. [PubMed Central: PMC5504311].

Featured Image:

Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments