Expression levels of FOXO1 and SMAD4 in esophageal cancer tissues and their relationships with clinicopathological features and prognosis

Objective To investigate the expression levels of FOXO1 and SMAD4 in esophageal cancer (EC) tissues and their associations with clinicopathological features and prognosis.

Methods Tissue samples of cancerous and adjacent non-cancerous tissues were collected from 131 EC patients. Hematoxylin-eosin (HE) staining was performed to observe the pathological morphology of EC and adjacent tissues. The mRNA expression of FOXO1 and SMAD4 was measured using quantitative real-time polymerase chain reaction (qRT-PCR), while the protein expression of FOXO1 and SMAD4 was determined by immunohistochemistry; Spearman's correlation analysis was employed to assess the correlation between FOXO1 and SMAD4 protein expression in EC tissues; Cox regression analysis was conducted to analyze factors influencing the prognosis of EC patients; Kaplan-Meier analysis was used to perform survival analysis for EC patients.

Results The expression of FOXO1 mRNA and its protein positive expression rate were significantly higher in the EC tissues than those in the adjacent tissues, whereas the expression of SMAD4 mRNA and its protein positive expression rate were significantly lower (P < 0.05). FOXO1 and SMAD4 were associated with tumor diameter, tumor differentiation, lymph node metastasis and TNM stage (P < 0.05). A negative correlation was observed between FOXO1 and SMAD4 protein expression in EC tissues (r=-0.419, P < 0.05). FOXO1, SMAD4, tumor diameter, differentiation, lymph node metastasis and TNM stage were identified as factors influencing mortality in EC patients (P < 0.05). The 3-year overall survival rate of EC patients was 84.73% (111/131). The 3-year cumulative survival rate was significantly lower in the EC patients with positive FOXO1 expression than in thosewith negative FOXO1 expression (P < 0.05), while it was significantly higher in patients with positive SMAD4 expression than in those with negative SMAD4 expression (P < 0.05).

Conclusion The positive expression rate of FOXO1 is higher, while that of SMAD4 is lower in EC tissues. Their protein expressions were associated with clinicopathological features and prognosis in EC patients. FOXO1 and SMAD4 may serve as important biomarkers for predicting the prognosis of EC.