Screening and identification of distant metastasis-related differentially expressed genes in human squamous cell lung carcinoma

Anat Rec (Hoboken). 2012 May;295(5):748-57. doi: 10.1002/ar.22441. Epub 2012 Mar 15.

Abstract

Distant metastasis is one of the leading causes of lung cancer death. Detecting the early-stage molecular alternations in primary tumors, such as gene expression differences, provides a "prognostic" value to the precaution of tumor metastasis. The aim of this article is to screen and identify the metastasis-related genes in human squamous cell lung carcinoma. Primary tumor tissues of nine patients with subsequent metastasis and eight patients without metastasis were selected to perform the gene microarray experiment. GO and pathway analyses were used to determine the differentially expressed genes. Two identified genes were further validated by real-time quantitative reverse transcription polymerase chain reaction (PCR) (real-time qRT-PCR). Two hundred and thirty-eight differentially expressed genes were detected in gene chip experiment, including 51 up-regulated genes and 187 down-regulated genes. These genes were involved in several cellular processes, including cell adhesion, cell cycle regulation, and apoptosis. GO analysis showed that the differentially expressed genes participated in a wide ranging of metastasis-related processes, including extracellular region and regulation of liquid surface tension. In addition, pathway analysis demonstrated that the differentially expressed genes were enriched in pathways related to cell cycle and Wnt signaling. Real-time qRT-PCR validation experiment of LCN2 and PDZK1IP1 showed a consistent up-regulation in the metastasis group. The metastasis of human squamous cell lung carcinoma is a complex process that is regulated by multiple gene alternations on the expression levels. The 238 differentially expressed genes identified in this study presumably contain a core set of genes involved in tumor metastasis. The real-time qRT-PCR results of PDZK1IP1 and LCN2 validated the reliability of this gene microarray experiment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology*
  • China
  • Cluster Analysis
  • Female
  • Gene Expression Profiling* / methods
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Genetic Predisposition to Disease
  • Humans
  • Lipocalin-2
  • Lipocalins / genetics
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors

Substances

  • Acute-Phase Proteins
  • Biomarkers, Tumor
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Membrane Proteins
  • PDZK1IP1 protein, human
  • Proto-Oncogene Proteins