Identification of miRNAs and differentially expressed genes in early phase non-small cell lung cancer

Tian,Wen; Liu,Jie; Pei,Baojing; Wang,Xiaobo; Guo,Yu; Yuan,Lin

doi:10.3892/or.2016.4561

Identification of miRNAs and differentially expressed genes in early phase non-small cell lung cancer

Authors:
- Wen Tian
- Jie Liu
- Baojing Pei
- Xiaobo Wang
- Yu Guo
- Lin Yuan
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Affiliations: Department of Internal Medicine-Oncology, Cangzhou Central Hospital, Cangzhou Municipality, Hebei 061000, P.R. China, Renqiu People's Hospital, Renqiu Municipality, Hebei 062550, P.R. China, Department of Orthopedics Department II, Cangzhou Central Hospital, Cangzhou Municipality, Hebei 061000, P.R. China, Hejian People's Hospital, Hejian Municipality, Cangzhou Municipality, Hebei 062450, P.R. China, Cangxian County Dulin Central Hospital, Cangxian County, Cangzhou Municipality, Hebei 061000, P.R. China
Published online on: January 14, 2016 https://doi.org/10.3892/or.2016.4561
Pages: 2171-2176

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Abstract

To explore the potential therapeutic targets of early‑stage non-small cell lung cancer (NSCLC), gene microarray analysis was conducted. The microarray data of NSCLC in stage IA, IB, IIA, and IIB (GSE50081), were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in IB vs. IA, IIA vs. IB, IIB vs. IIA were screened out via R. ToppGene Suite was used to get the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the DEGs. The GeneCoDis3 database and Cytoscape software were used to construct the transcriptional regulatory network. In total, 25, 17 and 14 DEGs were identified in IB vs. IA, IIA vs. IB, IIB vs. IIA of NSCLC, respectively. Some GO terms and pathways (e.g., extracellular space, alveolar lamellar body, bioactivation via cytochrome P450 pathway) were found significantly enriched in DEGs. Genes S100P, ALOX15B, CCL11, NLRP2, SERPINA3, FoxO4 and hsa-miR-491 may play important roles in the development of early-stage NSCLC. Thus, by bioinformatics analysis the key genes and biological processes involving in the development of early-stage NSCLC could be established, providing more potential references for the therapeutic targets.

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1	Farhat FS and Houhou W: Targeted therapies in non-small cell lung carcinoma: What have we achieved so far? Ther Adv Med Oncol. 5:249–270. 2013. View Article : Google Scholar : PubMed/NCBI
2	Tian ZQ, Li ZH, Wen SW, Zhang YF, Li Y, Cheng JG and Wang GY: Identification of commonly dysregulated genes in non-small-cell lung cancer by integrated analysis of microarray data and qRT-PCR validation. Lung. 193:583–592. 2015. View Article : Google Scholar : PubMed/NCBI
3	Liu Q, Yu Z, Xiang Y, Wu N, Wu L, Xu B, Wang L, Yang P, Li Y and Bai L: Prognostic and predictive significance of thymidylate synthase protein expression in non-small cell lung cancer: A systematic review and meta-analysis. Cancer Biomark. 15:65–78. 2015.
4	Wang Y, Chen J, Wu S, Hu C, Li X, Wang Y, Yang Y, Rajan N, Chen Y, Chen Y, et al: Clinical effectiveness and clinical toxicity associated with platinum-based doublets in the first-line setting for advanced non-squamous non-small cell lung cancer in Chinese patients: A retrospective cohort study. BMC Cancer. 14:9402014. View Article : Google Scholar : PubMed/NCBI
5	Tsai MF, Wang CC and Chen JJ: Tumour suppressor HLJ1: A potential diagnostic, preventive and therapeutic target in non-small cell lung cancer. World J Clin Oncol. 5:865–873. 2014. View Article : Google Scholar : PubMed/NCBI
6	Isa T, Tomita S, Nakachi A, Miyazato H, Shimoji H, Kusano T, Muto Y and Furukawa M: Analysis of microsatellite instability, K-ras gene mutation and p53 protein overexpression in intrahepatic cholangiocarcinoma. Hepatogastroenterology. 49:604–608. 2002.PubMed/NCBI
7	Gu A, Lu J, Wang W, Shi C, Han B and Yao M: Role of miR-497 in VEGF-A-mediated cancer cell growth and invasion in non-small cell lung cancer. Int J Biochem Cell Biol. 70:118–125. 2015. View Article : Google Scholar : PubMed/NCBI
8	Ma GF, Zhang RF, Ying KJ and Wang D: Effect evaluation of cisplatin-gemcitabine combination chemotherapy for advanced non-small cell lung cancer patients using microarray data. Eur Rev Med Pharmacol Sci. 19:578–585. 2015.PubMed/NCBI
9	Guo W, Xie L, Zhao L and Zhao Y: mRNA and microRNA expression profiles of radioresistant NCI-H520 non-small cell lung cancer cells. Mol Med Rep. 12:1857–1867. 2015.PubMed/NCBI
10	Der SD, Sykes J, Pintilie M, Zhu CQ, Strumpf D, Liu N, Jurisica I, Shepherd FA and Tsao MS: Validation of a histology-independent prognostic gene signature for early-stage, non-small-cell lung cancer including stage IA patients. J Thorac Oncol. 9:59–64. 2014. View Article : Google Scholar
11	Gautier L, Cope L, Bolstad BM and Irizarry RA: Affy - analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 20:307–315. 2004. View Article : Google Scholar : PubMed/NCBI
12	Diboun I, Wernisch L, Orengo CA and Koltzenburg M: Microarray analysis after RNA amplification can detect pronounced differences in gene expression using limma. BMC Genomics. 7:2522006. View Article : Google Scholar : PubMed/NCBI
13	Yan X, Jiang Z, Bi L, Yang Y and Chen W: Salvianolic acid A attenuates TNF-α- and D-GalN-induced ER stress-mediated and mitochondrial-dependent apoptosis by modulating Bax/Bcl-2 ratio and calcium release in hepatocyte LO2 cells. Naunyn Schmiedebergs Arch Pharmacol. 388:817–830. 2015. View Article : Google Scholar : PubMed/NCBI
14	Chen J, Bardes EE, Aronow BJ and Jegga AG: ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 37:W305–W311. 2009. View Article : Google Scholar : PubMed/NCBI
15	Nogales-Cadenas R, Carmona-Saez P, Vazquez M, Vicente C, Yang X, Tirado F, Carazo JM and Pascual-Montano A: GeneCodis: Interpreting gene lists through enrichment analysis and integration of diverse biological information. Nucleic Acids Res. 37:W317–W322. 2009. View Article : Google Scholar : PubMed/NCBI
16	Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B and Ideker T: Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498–2504. 2003. View Article : Google Scholar : PubMed/NCBI
17	Becker T, Gerke V, Kube E and Weber K: S100P, a novel Ca(2+)-binding protein from human placenta. cDNA cloning, recombinant protein expression and Ca²⁺ binding properties. Eur J Biochem. 207:541–547. 1992. View Article : Google Scholar : PubMed/NCBI
18	Zhang H, Wang G, Ding Y, Wang Z, Barraclough R, Rudland PS, Fernig DG and Rao Z: The crystal structure at 2A resolution of the Ca²⁺ -binding protein S100P. J Mol Biol. 325:785–794. 2003. View Article : Google Scholar : PubMed/NCBI
19	Bartling B, Rehbein G, Simm A, Silber RE and Hofmann HS: Porcupine expression is associated with the expression of S100P and other cancer-related molecules in non-small cell lung carcinoma. Int J Oncol. 36:1015–1021. 2010. View Article : Google Scholar : PubMed/NCBI
20	Magnusson LU, Lundqvist A, Karlsson MN, Skålén K, Levin M, Wiklund O, Borén J and Hultén LM: Arachidonate 15-lipoxygenase type B knockdown leads to reduced lipid accumulation and inflammation in atherosclerosis. PLoS One. 7:e431422012. View Article : Google Scholar : PubMed/NCBI
21	Tschopp J, Martinon F and Burns K: NALPs: A novel protein family involved in inflammation. Nat Rev Mol Cell Biol. 4:95–104. 2003. View Article : Google Scholar : PubMed/NCBI
22	Chan KS, Sano S, Kiguchi K, Anders J, Komazawa N, Takeda J and DiGiovanni J: Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis. J Clin Invest. 114:720–728. 2004. View Article : Google Scholar : PubMed/NCBI
23	Moore RJ, Owens DM, Stamp G, Arnott C, Burke F, East N, Holdsworth H, Turner L, Rollins B, Pasparakis M, et al: Mice deficient in tumor necrosis factor-α are resistant to skin carcinogenesis. Nat Med. 5:828–831. 1999. View Article : Google Scholar : PubMed/NCBI
24	Menzies-Gow A, Ying S, Sabroe I, Stubbs VL, Soler D, Williams TJ and Kay AB: Eotaxin (CCL11) and eotaxin-2 (CCL24) induce recruitment of eosinophils, basophils, neutrophils, and macrophages as well as features of early- and late-phase allergic reactions following cutaneous injection in human atopic and nonatopic volunteers. J Immunol. 169:2712–2718. 2002. View Article : Google Scholar : PubMed/NCBI
25	Campbell EM, Kunkel SL, Strieter RM and Lukacs NW: Temporal role of chemokines in a murine model of cockroach allergen-induced airway hyperreactivity and eosinophilia. J Immunol. 161:7047–7053. 1998.PubMed/NCBI
26	Yawalkar N, Uguccioni M, Schärer J, Braunwalder J, Karlen S, Dewald B, Braathen LR and Baggiolini M: Enhanced expression of eotaxin and CCR3 in atopic dermatitis. J Invest Dermatol. 113:43–48. 1999. View Article : Google Scholar : PubMed/NCBI
27	Xu MM, Mao GX, Liu J, Li JC, Huang H, Liu YF and Liu JH: Low expression of the FoxO4 gene may contribute to the phenomenon of EMT in non-small cell lung cancer. Asian Pac J Cancer Prev. 15:4013–4018. 2014. View Article : Google Scholar : PubMed/NCBI
28	Su L, Liu X, Chai N, Lv L, Wang R, Li X, Nie Y, Shi Y and Fan D: The transcription factor FOXO4 is down-regulated and inhibits tumor proliferation and metastasis in gastric cancer. BMC Cancer. 14:3782014. View Article : Google Scholar : PubMed/NCBI
29	Liu XQ, Tang SH, Zhang ZY and Jin HF: Expression and clinical significance of FOX04 in colorectal cancer. Chinese J Cell Mol Immunol. 27:969–971. 2011.In Chinese.
30	Salic K and De Windt LJ: MicroRNAs as biomarkers for myocardial infarction. Curr Atheroscler Rep. 14:193–200. 2012. View Article : Google Scholar : PubMed/NCBI
31	Huang WC, Chan SH, Jang TH, Chang JW, Ko YC, Yen TC, Chiang SL, Chiang WF, Shieh TY, Liao CT, et al: miRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell carcinoma invasion and metastasis. Cancer Res. 74:751–764. 2014. View Article : Google Scholar
32	Zhou Y, Li Y, Ye J, Jiang R, Yan H, Yang X, Liu Q and Zhang J: MicroRNA-491 is involved in metastasis of hepatocellular carcinoma by inhibitions of matrix metalloproteinase and epithelial to mesenchymal transition. Liver Int. 33:1271–1280. 2013. View Article : Google Scholar : PubMed/NCBI
33	Mowla SJ, Naeli P, Mirzadeh AF and Tavallaei M: Evaluating the expression of miR-491 as a potential stemness marker in lung tumor and non-tumor tissue. Cell J (Yakhteh). 15(Suppl 1): 632013.