Identification of differentially expressed genes between lung adenocarcinoma and lung squamous cell carcinoma by gene expression profiling

Lu,Chaojing; Chen,Hezhong; Shan,Zhengxiang; Yang,Lixin

doi:10.3892/mmr.2016.5420

Identification of differentially expressed genes between lung adenocarcinoma and lung squamous cell carcinoma by gene expression profiling

Authors:
- Chaojing Lu
- Hezhong Chen
- Zhengxiang Shan
- Lixin Yang
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Affiliations: Department of Thoracic Surgery, Changhai Hospital, Shanghai 200433, P.R. China
Published online on: June 22, 2016 https://doi.org/10.3892/mmr.2016.5420
Pages: 1483-1490
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to identify the differentially expressed genes (DEGs) between lung adenocarcinoma and normal lung tissues, and between lung squamous cell carcinoma and normal lung tissues, with the purpose of identifying potential biomarkers for the treatment of lung cancer. The gene expression profile (GSE6044) was downloaded from the Gene Expression Omnibus database, which included data from 10 lung adenocarcinoma samples, 10 lung squamous cell carcinoma samples, and five matched normal lung tissue samples. After data processing, DEGs were identified using the Student's t‑test adjusted via the Benjamini‑Hochberg method. Subsequently, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the DEGs was performed using the Database for Annotation, Visualization and Integrated Discovery, and a global network was constructed. A total of 95 upregulated and 241 downregulated DEGs were detected in lung adenocarcinoma samples, and 204 upregulated and 285 downregulated DEGs were detected in lung squamous cell carcinoma samples, as compared with the normal lung tissue samples. The DEGs in the lung squamous cell carcinoma group were enriched in the following three pathways: Hsa04110, Cell cycle; hsa03030, DNA replication; and hsa03430, mismatch repair. However, the DEGs in the lung adenocarcinoma group were not significantly enriched in any specific pathway. Subsequently, a global network of lung cancer was constructed, which consisted of 341 genes and 1,569 edges, of which the top five genes were HSP90AA1, BCL2, CDK2, KIT and HDAC2. The expression trends of the above genes were different in lung adenocarcinoma and lung squamous cell carcinoma when compared with normal tissues. Therefore, these genes were suggested to be crucial genes for differentiating lung adenocarcinoma and lung squamous cell carcinoma.

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1	Spruit MA, Janssen PP, Willemsen SC, Hochstenbag MM and Wouters EF: Exercise capacity before and after an 8-week multidisciplinary inpatient rehabilitation program in lung cancer patients: A pilot study. Lung Cancer. 52:257–260. 2006. View Article : Google Scholar : PubMed/NCBI
2	Inamura K, Fujiwara T, Hoshida Y, Isagawa T, Jones MH, Virtanen C, Shimane M, Satoh Y, Okumura S, Nakagawa K, et al: Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and non-negative matrix factorization. Oncogene. 24:7105–7113. 2005. View Article : Google Scholar : PubMed/NCBI
3	Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D and Bray F: Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer. 49:1374–1403. 2013. View Article : Google Scholar : PubMed/NCBI
4	Chang S, Dai M, Ren JS, Chen YH and Guo LW: Estimates and prediction on incidence, mortality and prevalence of lung cancer in China in 2008. Zhonghua Liu Xing Bing Xue Za Zhi. 33:391–394. 2012.In Chinese. PubMed/NCBI
5	Li S, Huang S and Peng SB: Overexpression of G protein-coupled receptors in cancer cells: Involvement in tumor progression. Int J Oncol. 27:1329–1339. 2005.PubMed/NCBI
6	Raponi M, Zhang Y, Yu J, Chen G, Lee G, Taylor JM, Macdonald J, Thomas D, Moskaluk C, Wang Y and Beer DG: Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung. Cancer Res. 66:7466–7472. 2006. View Article : Google Scholar : PubMed/NCBI
7	Sanchez-Palencia A, Gomez-Morales M, Gomez-Capilla JA, Pedraza V, Boyero L, Rosell R and Fárez-Vidal ME: Gene expression profiling reveals novel biomarkers in nonsmall cell lung cancer. Int J Cancer. 129:355–364. 2011. View Article : Google Scholar
8	Navab R, Strumpf D, Bandarchi B, Zhu CQ, Pintilie M, Ramnarine VR, Ibrahimov E, Radulovich N, Leung L, Barczyk M, et al: Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer. Proc Natl Acad Sci USA. 108:7160–7165. 2011. View Article : Google Scholar : PubMed/NCBI
9	Tsuta K, Tanabe Y, Yoshida A, Takahashi F, Maeshima AM, Asamura H and Tsuda H: Utility of 10 immunohistochemical markers including novel markers (desmocollin-3, glypican 3, S100A2, S100A7, and Sox-2) for differential diagnosis of squamous cell carcinoma from adenocarcinoma of the Lung. J Thorac Oncol. 6:1190–1199. 2011. View Article : Google Scholar : PubMed/NCBI
10	Hamamoto J, Soejima K, Yoda S, Naoki K, Nakayama S, Satomi R, Terai H, Ikemura S, Sato T, Yasuda H, et al: Identification of microRNAs differentially expressed between lung squamous cell carcinoma and lung adenocarcinoma. Mol Med Rep. 8:456–462. 2013.PubMed/NCBI
11	Liu J, Yang XY and Shi WJ: Identifying differentially expressed genes and pathways in two types of non-small cell lung cancer: Adenocarcinoma and squamous cell carcinoma. Genet Mol Res. 13:95–102. 2014. View Article : Google Scholar : PubMed/NCBI
12	Haynes W: Benjamini-Hochberg method. Encyclopedia of Systems Biology. Dubitzky W, Wolkenhauer O, Cho KH and Yokota H: Springer; New York, NY: pp. 782013, View Article : Google Scholar
13	Huang da W, Sherman BT and Lempicki RA: Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37:1–13. 2009. View Article : Google Scholar
14	Huang da W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009. View Article : Google Scholar : PubMed/NCBI
15	Peri S, Navarro JD, Amanchy R, Kristiansen TZ, Jonnalagadda CK, Surendranath V, Niranjan V, Muthusamy B, Gandhi TK, Gronborg M, et al: Development of human protein reference database as an initial platform for approaching systems biology in humans. Genome Res. 13:2363–2371. 2003. View Article : Google Scholar : PubMed/NCBI
16	Semënov MV and Snyder M: Human dishevelled genes constitute a DHR-containing multigene family. Genomics. 42:302–310. 1997. View Article : Google Scholar : PubMed/NCBI
17	Wei Q, Zhao Y, Yang ZQ, Dong QZ, Dong XJ, Han Y, Zhao C and Wang EH: Dishevelled family proteins are expressed in non-small cell lung cancer and function differentially on tumor progression. Lung Cancer. 62:181–192. 2008. View Article : Google Scholar : PubMed/NCBI
18	Wang J, Qian J, Hoeksema MD, Zou Y, Espinosa AV, Rahman SM, Zhang B and Massion PP: Integrative genomics analysis identifies candidate drivers at 3q26-29 amplicon in squamous cell carcinoma of the lung. Clin Cancer Res. 19:5580–5590. 2013. View Article : Google Scholar : PubMed/NCBI
19	Gao Q, Yang S and Kang MQ: Influence of survivin and Bcl-2 expression on the biological behavior of non-small cell lung cancer. Mol Med Rep. 5:1409–1414. 2012.PubMed/NCBI
20	Han ZX, Wang HM, Jiang G, Du XP, Gao XY and Pei DS: Overcoming paclitaxel resistance in lung cancer cells via dual inhibition of stathmin and Bcl-2. Cancer Biother Radiopharm. 28:398–405. 2013. View Article : Google Scholar : PubMed/NCBI
21	Zhang J, Wang S, Wang L, Wang R, Chen S, Pan B, Sun Y and Chen H: Prognostic value of Bcl-2 expression in patients with non-small-cell lung cancer: A meta-analysis and systemic review. Onco Targets Ther. 8:3361–3369. 2015. View Article : Google Scholar : PubMed/NCBI
22	Zhao XD, He YY, Gao J, Zhao C, Zhang LL, Tian JY and Chen HL: High expression of Bcl-2 protein predicts favorable outcome in non-small cell lung cancer: Evidence from a systematic review and meta-analysis. Asian Pac J Cancer Prev. 15:8861–8869. 2014. View Article : Google Scholar : PubMed/NCBI
23	Gallegos Ruiz MI, Floor K, Roepman P, Rodriguez JA, Meijer GA, Mooi WJ, Jassem E, Niklinski J, Muley T, van Zandwijk N, et al: Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target. PLoS One. 3:e00017222008. View Article : Google Scholar : PubMed/NCBI
24	Workman P, Burrows F, Neckers L and Rosen N: Drugging the cancer chaperone HSP90: Combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Ann NY Acad Sci. 1113:202–216. 2007. View Article : Google Scholar : PubMed/NCBI
25	Sequist LV, Gettinger S, Senzer NN, Martins RG, Jänne PA, Lilenbaum R, Gray JE, Iafrate AJ, Katayama R, Hafeez N, et al: Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J Clin Oncol. 28:4953–4960. 2010. View Article : Google Scholar : PubMed/NCBI
26	Li G, Qiu Y, Su Z, Ren S, Liu C, Tian Y and Liu Y: Genome-wide analyses of radioresistance-associated miRNA expression profile in nasopharyngeal carcinoma using next generation deep sequencing. PLoS One. 8:e844862013. View Article : Google Scholar : PubMed/NCBI
27	Hu S, Danilov AV, Godek K, Orr B, Tafe LJ, Rodriguez-Canales J, Behrens C, Mino B, Moran CA, Memoli VA, et al: CDK2 inhibition causes anaphase catastrophe in lung cancer through the centrosomal protein CP110. Cancer Res. 75:2029–2038. 2015. View Article : Google Scholar : PubMed/NCBI
28	Abrams TJ, Lee LB, Murray LJ, Pryer NK and Cherrington JM: SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther. 2:471–478. 2003.PubMed/NCBI
29	Geng L, Cuneo KC, Fu A, Tu T, Atadja PW and Hallahan DE: Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Cancer Res. 66:11298–11304. 2006. View Article : Google Scholar : PubMed/NCBI
30	Platta CS, Greenblatt DY, Kunnimalaiyaan M and Chen H: The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. J Surg Res. 142:219–226. 2007. View Article : Google Scholar : PubMed/NCBI
31	Komatsu N, Kawamata N, Takeuchi S, Yin D, Chien W, Miller CW and Koeffler HP: SAHA, a HDAC inhibitor, has profound anti-growth activity against non-small cell lung cancer cells. Oncol Rep. 15:187–191. 2006.