Objective
One of the main obstacles to treating patients with non-small-cell lung cancers
(NSCLC) is the emergence of drug resistance to epidermal growth factor receptor
(EGFR)-tyrosine kinase inhibitor (TKI) therapy.
Aim
To investigate the prognostic relevance of Runt-related transcription factor 1
(RUNX1) and Notch1 in NSCLC and to evaluate their potential involvement in
induction of epithelial-mesenchymal transition and resistance to EGFR-TKI
therapy.
Materials and methods
Immunohistochemical study of RUNX1, Notch1, E-cadherin, and hypoxiainducible
factor 1α (HIF-1α) was conducted upon 83 cases diagnosed as NSCLC.
The research was conducted in the departments of pathology, chest, and medical
oncology of the Faculty of Medicine, Benha University.
Results
A significant relation was found between RUNX1 and sex (P=0.001), smoking
history (P=0.002), and tumor grade (P=0.002). High RUNX1 expression was
associated with poor OS and DFS (P=0.003 and 0.005), respectively. Cases
with positive Notch1 expression were significantly associated with tumor grade
(P=0.005) and tumor stage (P=0.024). A significant association was detected
between Notch1 expression and poor OS and DFS (P=0.025 and 0.011),
respectively. A statistically significant correlation was found between RUNX1
and Notch1 expressions (P=0.040). Moreover, high RUNX1 and positive Notch1
expressions were significantly associated with negative E-cadherin and positive
HIF-1α expressions. Resistance against EGFR–TKI therapy was significantly
associated with high RUNX1, positive Notch1, negative E-cadherin, and positive
HIF-1α expressions, in EGFR-mutated cases.
Conclusions
RUNX1 and Notch1 may be involved in therapy resistance through the induction
of epithelial–mesenchymal transition and may serve as prognostic markers in
patients with NSCLC.