Fibrinogen is associated with EGFR mutation status and lymphatic metastasis in non-small cell lung cancer.

In the previous decade, tyrosine kinase inhibitors (TKIs) have demonstrated significant effects in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. However, sufficient tumor tissue for genetic testing cannot always be obtained in clinical settings. The present study evaluated whether fibrinogen may assist in predicting the EFGR mutation status in patients with NSCLC. Between January 2010 to December 2013, 303 patients with NSCLC underwent EGFR mutation testing. Plasma fibrinogen was acquired prior to treatment, and the associations between fibrinogen, EGFR mutation status and clinical features were assessed. A multivariate analysis and a receiver operator characteristic curve analysis were performed to identify the potential value of fibrinogen in predicting EGFR mutation status. The proportion of patients with hyperfibrinogenemia was significantly higher in N2 and N3 stages compared with N0 and N1 stages, 45.2 and 56.5 vs. 29.2 and 36.0%, respectively (P=0.001), and higher in the M1 stage compared with the M0 stage, 47.9 vs. 35.2%, respectively (P=0.025) (Stages according to the American Joint Committee of Cancer, 7th edition). Plasma fibrinogen levels were significantly lower in patients with EGFR mutations compared with the wild-type EGFR gene, 2.95 g/l (range, 0.84 -8.61 g/l) vs. 3.57 g/l (range, 1.38-7.44 g/l), respectively (P<0.001). In the multivariate analysis, logistic regression was utilized and the fibrinogen odds ratio (OR), 2.5, confidence intervals (CI) 1.53-4.51 (P<0.001) and smoking status OR 5.07, CI 3.01-8.53 (P<0.001), for which the area under the curve was 0.75, were revealed to be independent predictive factors. Hyperfibrinogenemia is associated with metastasis of the distant organs, but also metastasis of the lymphatic tissue. In addition, a multivariate model based on fibrinogen and smoking history may be used as a predictive marker of EGFR mutation status in patients with NSCLC.