EGFR Levels in NSCLC Are Associated With Expression of SATB1 and EMT-promoting Factors.

BACKGROUND/AIM: Epidermal growth factor receptor (EGFR) expression plays a key role in the diagnosis and treatment of non-small cell lung cancer (NSCLC). Therefore, identifying factors that may influence EGFR levels is of significant interest. Some studies have suggested that Special AT-rich Binding Protein 1 (SATB1) could act as a positive regulator of EGFR gene transcription; however, this relationship has not yet been confirmed in NSCLC. The aim of this study was to examine the potential association between EGFR and SATB1 expression at both the protein and mRNA levels in clinical NSCLC samples, and to evaluate these findings in relation to patients' clinicopathological data.

MATERIALS AND

METHODS

The study was conducted on 239 NSCLC clinical samples. We analyzed the level of EGFR, SATB1, SLUG, SNAIL, Twist1, N-cadherin, E-cadherin, and Ki67 proteins, as well as the expression of EGFR and SATB1 mRNAs. The methods used included immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH).

RESULTS

EGFR protein expression in the nuclei of NSCLC cells was positively associated both with the SATB1 level (Spearman's R=0.504; p≤0.0001) and with the expression of EMT-promoting factors SLUG (R=0.343; p≤0.01), SNAIL (R=0.129; p≤0.05), and Twist1 (R=0.249; p≤0.001). Similar relationships were observed also for the EGFR protein expressed in the cytoplasm of cancer cells. Moreover, it was revealed that EGFR mRNA expression was associated with NSCLC patient survival. In adenocarcinomas (ACs), high EGFR mRNA expression (>0.24 mRNA copies/cell) was correlated with significantly better overall survival (p=0.015), whereas in squamous cell carcinomas (LSCCs), high EGFR mRNA levels (>0.05 mRNA copies/cell) were associated with poor patients' prognosis (p=0.046).

CONCLUSION

EGFR protein expression in the nuclei and cytoplasm of NSCLC cells was positively associated with the expression of SATB1, SLUG, SNAIL, and Twist1 proteins. The prognostic significance of EGFR mRNA expression was dependent on tumor histology and differed significantly between the AC and LSCC samples.