title: Varied pathways of stage IA lung adenocarcinomas discovered by integrated gene expression analysis.
abstract: BACKGROUND
  Discovery of the progression-associated genes and pathways in lung adenocarcinoma (LAD) has important implications in understanding the molecular mechanism of tumor development. However, few studies had been performed to focus on the changes of pathways in lung adenocarcinoma development using microarray expression profile.
  
  
  RESULTS
  We performed a meta-analysis of 4 LAD microarray datasets encompassing 353 patients to reveal differentially expressed genes (DEGs) between normal lung tissues and LAD of different stages. Overall, 1 838 genes were found to be dys-regulated, and the adipogenesis, circadian rhythm, and Id pathways were significantly changed. Interestingly, most of the genes from the same gene family (such as Interleukin receptor, Matrix metallopeptidase, Histone cluster and Minichromosome maintenance complex component families) were found to be up-regulated (or down-regulated). Real-time PCR (qRT-PCR) was applied to validate the expression of randomly selected 18 DEGs in LAD cell lines. In the pathway analysis among stages, Oxidative stress, Glycolysis/Gluconeogenesis and Integrin-mediated cell adhesion pathways, which were involved in cancer cell proliferation and metastasis, were showed to be significantly regulated in stages other than IA.
  
  
  CONCLUSIONS
  Genes involved in adipogenesis and Id pathways might play important roles in development of LADs. The similar trend of expression of the gene family members suggested coordinate regulation in tumor progression. Three pathways (Oxidative stress, Glycolysis/Gluconeogenesis and Integrin-mediated cell adhesion pathways) significantly regulated in stages other than stage IA suggested that genes and pathways conferring invasive character might be activated in the preinvasive stage IB, while the Oxidative stress and the Glycolysis/Gluconeogenesis pathways might have strong connections to cisplatin-based chemotherapy. The insignificantly regulated three pathways in stage IA might be used in early-stage detection of LAD.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Chengwen
authors.initials: C
authors.lastname: Chen
authors.forename: Xuping
authors.initials: X
authors.lastname: Fu
authors.forename: Deqiang
authors.initials: D
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D018401:Sample Size