The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis

Cancer Biol Ther. 2015;16(7):1019-28. doi: 10.1080/15384047.2015.1046649. Epub 2015 May 15.

Abstract

Purpose: The RET fusion gene is a novel oncogene observed in a subset of NSCLC in recent years. Nevertheless, the results of epidemiological studies concerning the gene remain unclear. Thus, a meta-analysis was conducted to evaluate the correlation of RET fusion gene with demographic and clinicopathological features of NSCLC.

Methods: PubMed, Embase, and Web of Science databases were searched to identify eligible studies. The association of RET fusion gene occurrence with gender, age, smoking status, histology type and tumor stage were analyzed in meta-analysis. Subgroup analysis according to patients' location (Asian and non-Asian) was also conducted. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the correlation.

Results: Nine studies with a total of 6,899 NSCLC patients met the inclusion criteria. A total of 84 patients with RET fusion gene were detected. The RET fusion gene was identified at significantly higher frequencies in female (OR = 0.55, 95%CI = 0.35-0.85) than male patients and in young (<60) patients (OR = 0.43, 95%CI = 0.19-0.99) than old patients (≤60), particularly in patients from Asian. A significant higher frequency was also identified in non-smokers (OR = 0.28, 95% CI = 0.16-0.49), and in patients with lung adenocarcinomas (OR = 3.59, 95%CI = 1.50-8.56). Additionally, no association between RET fusion gene and the TNM stage of tumor was observed.

Conclusion: RET fusion gene occurred predominantly in Asian females with younger age, in non-smokers, and in lung adenocarcinomas patients. This subset of NSCLC patients might be good candidates for personalized diagnostic and therapeutic approaches.

Keywords: ADC, Adenocarcinoma; ARTN, Artemin; CIs, Confidence Intervals; EGFR, Epidermal Growth Factor Receptor; GDNF, Glial cell line-derived Neurotrophic Factor; NADC, Non-adenocarcinoma; NRTN, Neurturin; NSCLC, Non-Small Cell Lung Cancer; OR, Odd Ratio; PI3K, Phosphatidylinositol 3-kinase; PSPN, Persephin; RET; RT-PCR, Real-Time Polymerase Chain Reaction; SCLC, Small-cell lung cancer; TKIs, Tyrosine Kinase Inhibitors; clinicopathological features; demographic features; fusion; meta-analysis; non-small cell lung cancer; targeted therapy.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / ethnology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Age Factors
  • Asian People / genetics
  • Carcinoma, Non-Small-Cell Lung / ethnology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • China
  • Cytoskeletal Proteins / genetics
  • Female
  • Gene Frequency
  • Humans
  • Japan
  • Lung Neoplasms / ethnology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Nuclear Receptor Coactivators / genetics
  • Odds Ratio
  • Oncogene Proteins, Fusion / genetics*
  • Proto-Oncogene Proteins c-ret / genetics*
  • Republic of Korea
  • Sex Factors
  • Smoking / ethnology
  • Smoking / genetics
  • Transcription Factors / genetics

Substances

  • CCDC6 protein, human
  • Cytoskeletal Proteins
  • KIF5B-RET fusion protein, human
  • NCOA4 protein, human
  • Nuclear Receptor Coactivators
  • Oncogene Proteins, Fusion
  • TRIM33 protein, human
  • Transcription Factors
  • Proto-Oncogene Proteins c-ret
  • RET protein, human