Original Article
The clinical significance of loss of FHIT and PTEN expression in 289 patients with non-small-cell lung cancer
Abstract
Background: The Fragile histidine triad (FHIT) gene is a nucleotide metabolism associated with the Ap3A hydrolase, which may regulate cell cycle and induce cell apoptosis. Phosphate and tensin homolog deleted on chromosome ten (PTEN) had been found to be a dual specificity phosphatase activity (DSP) of the tumor suppressor gene. However, the roles of FHIT and PTEN in patients with non-small-cell lung cancer (NSCLC) is not well established so far.
Methods: Immunohistochemistry staining was used to determine the expression of FHIT and PTEN in 76 cases of normal lung tissue and benign pulmonary lesion tissues and 289 cases of NSCLC.
Results: The negative rate of FHIT and PTEN expression in NSCLC was significantly higher than that in normal lung tissues and benign pulmonary lesion tissues (P<0.001). The negative expression of FHIT and PTEN was closely associated with cell differentiation, TNM stages and lymph node metastasis and smoking history in NSCLC (P<0.001). Furthermore, the expressing level of FHIT and PTEN protein in NSCLC was associated with a poor survival of patients (P<0.001). The result of multivariate Cox analysis showed that smoking, TNM stage and loss of FHIT and PTEN expression were independent prognosticators.
Conclusions: Loss of FHIT and PTEN expression in clinical specimens could be related to invasion and metastasis of NSCLC. FHIT and PTEN expression are independent prognostic factor for patients with NSCLC. Restoring the imbalance of FHIT and PTEN expression may become a new target to treat NSCLC. In addition, tobacco can induce gene deletion mutations and result in the loss of FHIT expression.
Methods: Immunohistochemistry staining was used to determine the expression of FHIT and PTEN in 76 cases of normal lung tissue and benign pulmonary lesion tissues and 289 cases of NSCLC.
Results: The negative rate of FHIT and PTEN expression in NSCLC was significantly higher than that in normal lung tissues and benign pulmonary lesion tissues (P<0.001). The negative expression of FHIT and PTEN was closely associated with cell differentiation, TNM stages and lymph node metastasis and smoking history in NSCLC (P<0.001). Furthermore, the expressing level of FHIT and PTEN protein in NSCLC was associated with a poor survival of patients (P<0.001). The result of multivariate Cox analysis showed that smoking, TNM stage and loss of FHIT and PTEN expression were independent prognosticators.
Conclusions: Loss of FHIT and PTEN expression in clinical specimens could be related to invasion and metastasis of NSCLC. FHIT and PTEN expression are independent prognostic factor for patients with NSCLC. Restoring the imbalance of FHIT and PTEN expression may become a new target to treat NSCLC. In addition, tobacco can induce gene deletion mutations and result in the loss of FHIT expression.
