Galectin expression profiling identifies galectin-1 and Galectin-9Δ5 as prognostic factors in stage I/II non-small cell lung cancer

PLoS One. 2014 Sep 26;9(9):e107988. doi: 10.1371/journal.pone.0107988. eCollection 2014.

Abstract

Approximately 30-40% of the patients with early stage non-small cell lung cancer (NSCLC) will present with recurrent disease within two years of resection. Here, we performed extensive galectin expression profiling in a retrospective study using frozen and paraffin embedded tumor tissues from 87 stage I/II NSCLC patients. Our data show that galectin mRNA expression in NSCLC is confined to galectin-1, -3, -4, -7, -8, and -9. Next to stage, univariable Cox regression analysis identified galectin-1, galectin-9FL and galectin-9Δ5 as possible prognostic markers. Kaplan-Meier survival estimates revealed that overall survival was significantly shorter in patients that express galectin-1 above median levels, i.e., 23.0 (2.9-43.1) vs. 59.9 (47.7-72.1) months (p = 0.020) as well as in patients that express galectin-9Δ5 or galectin-9FL below the median, resp. 59.9 (41.9-75.9) vs. 32.8 (8.7-56.9) months (p = 0.014) or 23.2 (-0.4-46.8) vs. 58.9 (42.9-74.9) months (p = 0.042). All three galectins were also prognostic for disease free survival. Multivariable Cox regression analysis showed that for OS, the most significant prognostic model included stage, age, gal-1 and gal-9Δ5 while the model for DFS included stage, age and gal-9Δ5. In conclusion, the current study confirms the prognostic value of galectin-1 and identifies galectin-9Δ5 as novel potential prognostic markers in early stage NSCLC. These findings could help to identify early stage NSCLC patients that might benefit most from adjuvant chemotherapy.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Female
  • Galectin 1 / genetics*
  • Galectin 1 / metabolism
  • Galectins / genetics*
  • Galectins / metabolism
  • Gene Expression
  • Gene Expression Profiling*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Retrospective Studies
  • Risk Factors

Substances

  • Galectin 1
  • Galectins
  • LGALS9 protein, human
  • RNA, Messenger

Grants and funding

This work was supported by grants from the Dutch Cancer Society (www.kwfkankerbestrijding.nl:UM2008-4101; VU2009-4358) to AWG and VLT. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.