Expression of STAT5, COX-2 and PIAS3 in correlation with NSCLC histhopathological features

PLoS One. 2014 Aug 19;9(8):e104265. doi: 10.1371/journal.pone.0104265. eCollection 2014.

Abstract

Signal transducers and activators of transcription (STATs), their inhibitors and cyclooxygenase-2 (COX-2) participate in transformations of many various types of cancers. The aim of the present study was to evaluate the relationship between STAT5A/B, COX-2, and PIAS3 mRNA expression and tumor staging, metastasis status, and histopathological subtype in 71 patients with confirmed non-small cell lung cancer (NSCLC) diagnosis. Total RNA was isolated from NSCLC tissue samples and the expression of the studied genes was assessed using TaqMan probes in real-time PCR assay. The expression levels of STAT5A, STAT5B, and COX-2 genes were increased in 69%, 79%, and 71% NSCLC samples respectively, while PIAS3 expression was decreased in the majority (69%) of the studied tissues. Statistically significant differences were observed between STAT5 isoforms (P = 0.0008), with higher expression of STAT5B. We found statistically significant positive correlation between STAT5B and COX-2 (rho = 0.045), and significant negative correlation between STAT5B and PIAS3 (rho = -0.049). The negative correlation between STAT5B and PIAS3 (rho = -0.43) was also observed in T2a+T2b tumor group. Additionally, STAT5B and COX-2 expression levels were significantly different between T1a+T1b and T2a+T2b tumors (P = 0.002 and P = 0.041, respectively), with higher expression of both genes in T2 tumor stage. PIAS3 expression was significantly lower in NSCC subtype as compared with SCC subtype (P = 0.017). Also, STAT5A and STAT5B immunoexpression was assessed, and the results indicated significantly higher protein levels in NSCLC patients as compared with controls (P = 0.048 and P = 0.034, respectively). High STAT5B immunoexpression was positively correlated with STAT5B gene expression in tumors (rho = 0.755). STAT5B protein level was also significantly higher in T2a+T2b tumors, reflecting high STAT5B gene expression in this group. There was no statistically significant association between mRNA and protein expression levels of the studied genes and patients' characteristics: age, gender, smoking. The obtained results highlight the importance of the genes STAT5B and COX-2 in lung cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Cyclooxygenase 2 / genetics*
  • Cyclooxygenase 2 / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Molecular Chaperones / genetics*
  • Molecular Chaperones / metabolism
  • Neoplasm Staging
  • Protein Inhibitors of Activated STAT / genetics*
  • Protein Inhibitors of Activated STAT / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Risk Factors
  • STAT5 Transcription Factor / genetics*
  • STAT5 Transcription Factor / metabolism
  • Smoking / physiopathology

Substances

  • Molecular Chaperones
  • PIAS3 protein, human
  • Protein Inhibitors of Activated STAT
  • Protein Isoforms
  • RNA, Messenger
  • STAT5 Transcription Factor
  • Cyclooxygenase 2
  • PTGS2 protein, human

Grants and funding

The study was supported by the Medical University of Lodz, Poland (grant no 502/03-1-151/04/502-14-069). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.