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

L. Cicchillitti, G. Corrado, M. Carosi, M. E. Dabrowska, R. Loria, R. Falcioni, G. Cutillo, G. Piaggio, E. Vizza

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)7935-7945
Number of pages11
JournalOncotarget
Volume8
Issue number5
DOIs
Publication statusPublished - 2017

Keywords

  • NF-Y
  • endometrial cancer
  • estrogen receptor
  • lamin A
  • miR-200 family

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