Prognostic role of NF-YA splicing isoforms and Lamin A status in low grade endometrial cancer

Oncotarget. 2017 Jan 31;8(5):7935-7945. doi: 10.18632/oncotarget.13854.

Abstract

Although most cases of low grade (G1) endometrial cancer (EC) do not behave aggressively, in rare instances, can progress in a highly aggressive manner. In this study we analyzed formalin-fixed, paraffin-embedded (FFPE) EC tissues to find novel clinical and biological features to help diagnosis and treatment of G1 ECs s in order to better stratify patient risk of recurrence. A retrospective cohort of FFPE specimens from patients with EC (n=87) and benign tissue specimens (NE) from patients who underwent a hysterectomy to treat other benign disease (n = 13) were collected. Total RNA and proteins were extracted and analyzed, respectively, by quantitative PCR and western blotting. NF-YAs is expressed and lamin A is down-modulated in all high grade (G2 and G3) ECs. In G1 ECs, NF-YAs expression is heterogeneous being expressed only in a subset of these tumours. Interestingly, the G1 ECs that express NF-YAs display low levels of lamin A similar to those present in G2 and G3 ECs. Of note, this pattern of NF-YAs and lamin A expression correlates with tumor aggressiveness assessed by comparative analysis with estrogen receptor (ER) status and epithelial-mesenchymal transition (EMT) markers thus suggesting its potential role as biomarker of tumour aggressiveness in G1 EC. In all grade ECs, lamin A is strongly downmodulated, being its expression inversely correlated with tumor aggressiveness and its loss of expression. We identified NF-YAs and lamin A expression levels as novel potential biomarkers useful to identify G1 ECs patients with risk of recurrence.

Keywords: NF-Y; endometrial cancer; estrogen receptor; lamin A; miR-200 family.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • CCAAT-Binding Factor / analysis*
  • CCAAT-Binding Factor / genetics
  • Endometrial Neoplasms / chemistry*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / surgery
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hysterectomy
  • Lamin Type A / analysis*
  • Lamin Type A / genetics
  • Middle Aged
  • Neoplasm Grading
  • Protein Isoforms
  • RNA, Messenger / genetics
  • Receptors, Estrogen / analysis
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • CCAAT-Binding Factor
  • Lamin Type A
  • NFYA protein, human
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Estrogen