Identification of TNM stage-specific genes in lung adenocarcinoma by genome-wide expression profiling

Liu,Ming; Pan,Hong; Zhang,Feng; Zhang,Yongbiao; Zhang,Yang; Xia,Han; Zhu,Jing; Fu,Weiling; Zhang,Xiaoli

doi:10.3892/ol.2013.1469

Identification of TNM stage-specific genes in lung adenocarcinoma by genome-wide expression profiling

Authors:
- Ming Liu
- Hong Pan
- Feng Zhang
- Yongbiao Zhang
- Yang Zhang
- Han Xia
- Jing Zhu
- Weiling Fu
- Xiaoli Zhang
View Affiliations

Affiliations: Department of Cardiothoracic Surgery, Affiliated Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China, Department of Laboratory Diagnostics, Affiliated South‑West Hospital, Third Military Medical University, Chongqing 400038, P.R. China, Beijing Institute of Genomics of the Chinese Academy of Sciences, Beijing Genomics Institute, Beijing Proteomics Institute, Beijing 100029, P.R. China, Department of Laboratory Diagnostics, The First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, P.R. China
Published online on: July 15, 2013 https://doi.org/10.3892/ol.2013.1469
Pages: 763-768

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to investigate the molecular basis of lung cancer development using a microarray to identify the differentially‑expressed genes associated with the various tumor‑node‑metastasis (TNM) stages of lung adenocarcinoma. This subtype of lung cancer has increased in incidence within recent years in China. A 35K oligo gene array covering ~25,100 genes was used to screen the differentially‑expressed genes among 90 lung adenocarcinoma samples of various TNM stages. To verify the data from the gene arrays, three genes [human zinc finger‑containing, Miz1, PIAS‑like protein on chromosome 7 (Zimp7), GINS complex subunit 2 (GINS2) and NSAID activated gene 1 (NAG‑1)] were validated using quantitative (q)PCR in an alternative set of samples to the gene array. A total of 640 genes were identified that were differentially‑expressed in lung adenocarcinoma compared with the surrounding normal lung tissues. From these 640 candidate genes, 10 were observed to be differentially‑expressed among TNM stages I, II and IIIA, of which, the Zimp7, GINS2 and NAG‑1 genes were reported for the first time to be expressed at high levels in lung adenocarcinoma. The results of the qPCR for the three genes were consistent with those from the gene array. In total, 10 candidate genes were identified to be associated with the various TNM stages of lung adenocarcinoma in the population studied, which may provide new insights into the molecular basis underlying the development of lung adenocarcinoma and offer new targets for the diagnosis, therapy and prognosis.

View Figures

View References

1	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar
2	Singhal S, Miller D, Ramalingam S and Sun SY: Gene expression profiling of non-small cell lung cancer. Lung Cancer. 60:313–324. 2008. View Article : Google Scholar : PubMed/NCBI
3	Hofmann HS, Bartling B, Simm A, et al: Identification and classification of differentially expressed genes in non-small cell lung cancer by expression profiling on a global human 59.620-element oligonucleotide array. Oncol Rep. 16:587–595. 2006.PubMed/NCBI
4	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
5	Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29:e452001. View Article : Google Scholar : PubMed/NCBI
6	Loda M, Capodieci P, Mishra R, et al: Expression of mitogen-activated protein kinase phosphatase-1 in the early phases of human epithelial carcinogenesis. Am J Pathol. 149:1553–1564. 1996.PubMed/NCBI
7	Zhang L, Zhou W, Velculescu VE, et al: Gene expression profiles in normal and cancer cells. Science. 276:1268–1272. 1997. View Article : Google Scholar : PubMed/NCBI
8	Tai CJ, Wu AT, Chiou JF, et al: The investigation of mitogen-activated protein kinase phosphatase-1 as a potential pharmacological target in non-small cell lung carcinomas, assisted by non-invasive molecular imaging. BMC Cancer. 10:952010. View Article : Google Scholar
9	Huang CY, Beliakoff J, Li X, et al: hZimp7, a novel PIAS-like protein, enhances androgen receptor-mediated transcription and interacts with SWI/SNF-like BAF complexes. Mol Endocrinol. 19:2915–2929. 2005. View Article : Google Scholar : PubMed/NCBI
10	Hanissian SH, Akbar U, Teng B, et al: cDNA cloning and characterization of a novel gene encoding the MLF1-interacting protein MLF1IP. Oncogene. 23:3700–3707. 2004. View Article : Google Scholar : PubMed/NCBI
11	Thomassen M, Tan Q and Kruse TA: Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis. Breast Cancer Res Treat. 113:239–249. 2009. View Article : Google Scholar : PubMed/NCBI
12	Ishikawa N, Takano A, Yasui W, et al: Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas. Cancer Res. 67:11601–11611. 2007. View Article : Google Scholar : PubMed/NCBI
13	Matsuda R, Enokida H, Chiyomaru T, et al: LY6K is a novel molecular target in bladder cancer on basis of integrate genome-wide profiling. Br J Cancer. 104:376–386. 2011. View Article : Google Scholar : PubMed/NCBI
14	Kim KS, Baek SJ, Flake GP, Loftin CD, Calvo BF and Eling TE: Expression and regulation of nonsteroidal anti-inflammatory drug-activated gene (NAG-1) in human and mouse tissue. Gastroenterology. 122:1388–1398. 2002. View Article : Google Scholar : PubMed/NCBI
15	Newman D, Sakaue M, Koo JS, et al: Differential regulation of nonsteroidal anti-inflammatory drug-activated gene in normal human tracheobronchial epithelial and lung carcinoma cells by retinoids. Mol Pharmacol. 63:557–564. 2003. View Article : Google Scholar : PubMed/NCBI
16	Boyle GM, Pedley J, Martyn AC, et al: Macrophage inhibitory cytokine-1 is overexpressed in malignant melanoma and is associated with tumorigenicity. J Invest Dermatol. 129:383–391. 2009. View Article : Google Scholar : PubMed/NCBI
17	Brown DA, Ward RL, Buckhaults P, et al: MIC-1 serum level and genotype: associations with progress and prognosis of colorectal carcinoma. Clin Cancer Res. 9:2642–2650. 2003.PubMed/NCBI
18	Sienel W, Varwerk C, Linder A, et al: Melanoma associated antigen (MAGE)-A3 expression in Stages I and II non-small cell lung cancer: results of a multi-center study. Eur J Cardiothorac Surg. 25:131–134. 2004. View Article : Google Scholar : PubMed/NCBI
19	Tano K, Mizuno R, Okada T, et al: MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS Lett. 584:4575–4580. 2010. View Article : Google Scholar : PubMed/NCBI
20	Ji P, Diederichs S, Wang W, et al: MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 22:8031–8041. 2003. View Article : Google Scholar : PubMed/NCBI
21	Nabeshima K, Inoue T, Shimao Y and Sameshima T: Matrix metalloproteinases in tumor invasion: role for cell migration. Pathol Int. 52:255–264. 2002. View Article : Google Scholar : PubMed/NCBI
22	Hofmann HS, Hansen G, Richter G, et al: Matrix metalloproteinase-12 expression correlates with local recurrence and metastatic disease in non-small cell lung cancer patients. Clin Cancer Res. 11:1086–1092. 2005.PubMed/NCBI