Correlation Between Raf/MEK/ERK Signaling Pathway and Clinicopathological Features and Prognosis for Patients With Breast Cancer Having Axillary Lymph Node Metastasis

OBJECTIVE This study aims to investigate the correlations between rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase signaling pathway and clinicopathological features and prognosis for patients with breast cancer having axillary lymph node metastasis. METHODS A total of 118 breast cancer tissues with axillary lymph node metastasis (axillary lymph node metastasis group), 150 breast cancer tissues with non-axillary lymph node metastasis (non-axillary lymph node metastasis group), and 216 normal breast tissues (normal group) were enrolled in this study. The messenger RNA and protein expressions of rapidly accelerated fibrosarcoma, MEK, extracellular signal-regulated kinase, and their phosphorylated (p-) proteins were examined by reverse transcriptase quantitative polymerase chain reaction and immunohistochemistry, respectively. All patients received a 1-year follow-up, and the clinical follow-up data were collected. The multiple factors on the prognosis of patients with breast cancer having axillary lymph node metastasis were tested by Cox regression analysis. RESULTS The messenger RNA expressions of rapidly accelerated fibrosarcoma, MEK, and extracellular signal-regulated kinase and positive rates of rapidly accelerated fibrosarcoma, MEK, phosphorylated MEK, extracellular signal-regulated kinase, and p-extracellular signal-regulated kinase in the axillary lymph node metastasis group were higher than in the non-axillary lymph node metastasis and normal groups (all P < .05). The protein expressions of rapidly accelerated fibrosarcoma, MEK, phosphorylated MEK, extracellular signal-regulated kinase, and p-extracellular signal-regulated kinase were associated with tumor size, clinical stage, and axillary lymph node metastasis number (all P < .05). Rapidly accelerated fibrosarcoma, MEK, and extracellular signal-regulated kinase expressions were significantly correlated with the prognosis of patients with breast cancer (all P < .05). Patients with BC having positive rapidly accelerated fibrosarcoma, MEK, phosphorylated MEK, extracellular signal-regulated kinase, and phosphorylated ERK expressions had a higher survival rate than patients with BC having the negative ones (all P < .05). Rapidly accelerated fibrosarcoma and extracellular signal-regulated kinase protein expressions, clinical stage, pathological grade, and axillary lymph node metastasis number were independent prognostic factors in patients with breast cancer having axillary lymph node metastasis (all P < .05). CONCLUSION Our study proved that rapidly accelerated fibrosarcoma/MEK/extracellular signal-regulated kinase signaling pathway is significantly correlated with the clinicopathological features and prognosis for patients with BC having axillary lymph node metastasis. Rapidly accelerated fibrosarcoma and extracellular signal-regulated kinase protein expressions are independent prognostic factors for patients with breast cancer having axillary lymph node metastasis.