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

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.

Diagnostic and prognostic value of serum interleukin-16 in patients with gastric cancer

“…Western blotting. IL-16 protein level was analyzed by western blotting assay according a previous study (13,15). Proteins were extracted in cell lysis buffer (89900; Thermo Fisher Scientific, Inc.) on ice followed by centrifugation at 12,000 x g for 10 min at 4˚C, then boiled at 100˚C for 10 min.…”

Transcription Factors in Cancer: When Alternative Splicing Determines Opposite Cell Fates

“…In endometrial tissues, the exclusive presence of NF-YAl observed in benign samples suggested that it may represent a marker of differentiation, in opposition to NF-YAs, which is expressed into cancer tissues and linked to poorly differentiated cells [26]. In breast and lung cancers, the ratio Cells 2020, 9, 760 4 of 28 between NF-YAl/NF-YAs isoforms is dramatically shifted towards NF-YAs [27,28].…”

Revealing elasticity of largely deformed cells flowing along confining microchannels

“…MDA-MB-231) undergone epithelial-mesenchymal transition (EMT) usually contain soer nuclei. [52][53][54] Hence the nal modulus E f and modulus jump DE could provide the insightful information of the physical distortion (either stiffening or enlarging) of the nuclei.…”