Downregulation of Ras GTPase‑activating protein 1 is associated with poor survival of breast invasive ductal carcinoma patients.

Abstract

Ras GTPase‑activating protein 1 (RASA1) functions to inactivate Ras‑GTPase and inhibit the mitogenic signal. Reduction or loss of RASA1 expression occurs during human cancer development and progression. This study investigated RASA1 expression in normal and breast cancer tissue specimens to determine the association with prognosis of breast cancer patients. Two sets of patient samples (45 fresh tissues and 373 paraffin‑embedded tissues) were analyzed for RASA1 expression using RT‑qPCR and immunohisto-chemistry. The results showed that the expression of RASA1 mRNA was lower in breast cancer tissues than in the corresponding normal tissues (P<0.001). Additionally, RASA1 expression was reduced in 60.6% (226/373) of breast cancer tissues. The reduced RASA1 expression was significantly associated with tumor lymph node metastasis (P=0.002), advanced TNM stages (P=0.017), estrogen receptor (ER) expression (P=0.002), Ki‑67 (P=0.009), higher histological grade (P<0.001), and triple‑negative breast cancer (P=0.041). Moreover, the reduced RASA1 expression was associated with shorter disease‑free survival (P=0.036) and overall survival (P<0.001) of breast cancer patients. RASA1 expression, together with tumor lymph‑node metastasis, TNM stage, Her‑2 expression, and triple‑negative breast cancer were independent factors in predicting survival of breast cancer patients. In conclusion, RASA1 expression is frequently reduced in breast cancer tissues, and the reduced RASA1 expression is associated with breast cancer progression and poor survival and disease‑free survival of patients.