Gene expression profiling in human lung development: an abundant resource for lung adenocarcinoma prognosis

PLoS One. 2014 Aug 20;9(8):e105639. doi: 10.1371/journal.pone.0105639. eCollection 2014.

Abstract

A tumor can be viewed as a special "organ" that undergoes aberrant and poorly regulated organogenesis. Progress in cancer prognosis and therapy might be facilitated by re-examining distinctive processes that operate during normal development, to elucidate the intrinsic features of cancer that are significantly obscured by its heterogeneity. The global gene expression signatures of 44 human lung tissues at four development stages from Asian descent and 69 lung adenocarcinoma (ADC) tissue samples from ethnic Chinese patients were profiled using microarrays. All of the genes were classified into 27 distinct groups based on their expression patterns (named as PTN1 to PTN27) during the developmental process. In lung ADC, genes whose expression levels decreased steadily during lung development (genes in PTN1) generally had their expression reactivated, while those with uniformly increasing expression levels (genes in PTN27) had their expression suppressed. The genes in PTN1 contain many n-gene signatures that are of prognostic value for lung ADC. The prognostic relevance of a 12-gene demonstrator for patient survival was characterized in five cohorts of healthy and ADC patients [ADC_CICAMS (n = 69, p = 0.007), ADC_PNAS (n = 125, p = 0.0063), ADC_GSE13213 (n = 117, p = 0.0027), ADC_GSE8894 (n = 2, p = 0.01), and ADC_NCI (n = 282, p = 0.045)] and in four groups of stage I patients [ADC_CICAMS (n = 22, p = 0.017), ADC_PNAS (n = 76, p = 0.018), ADC_GSE13213 (n = 79, p = 0.02), and ADC_qPCR (n = 62, p = 0.006)]. In conclusion, by comparison of gene expression profiles during human lung developmental process and lung ADC progression, we revealed that the genes with a uniformly decreasing expression pattern during lung development are of enormous prognostic value for lung ADC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung / embryology
  • Lung / metabolism*
  • Lung / pathology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Prognosis
  • Transcriptome*

Associated data

  • GEO/GSE43767

Grant support

This work was supported by the National High Technology Research and Development Program of China (2012AA02A502 and 2014AA020602) received by YG and SC, respectively; and the Capital Citizen Health Project (Z111107067311018) received by SC; and the National Natural Science Foundation of China (81201592) received by LF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.