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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Fibrinogen is associated with EGFR mutation status and lymphatic metastasis in non-small cell lung cancer
Jian Guan1, Nan Xiao1, Chun Qiu1
1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Abstract:
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.
Insights
Plasma fibrinogen levels can help predict epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC) patients when tissue is insufficient. A model combining fibrinogen and smoking history shows promise as a predictive marker.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tyrosine kinase inhibitors (TKIs) are effective for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.
- Obtaining sufficient tumor tissue for genetic testing in NSCLC can be challenging in clinical practice.
- Biomarkers are needed to predict EGFR mutation status when tissue biopsy is not feasible.
Purpose of the Study:
- To evaluate the potential of plasma fibrinogen levels as a predictive marker for EGFR mutation status in NSCLC patients.
- To assess the association between fibrinogen levels, EGFR mutation status, and clinical features in NSCLC.
- To determine if fibrinogen can serve as a surrogate marker for EGFR mutation status, especially when tissue is limited.
Main Methods:
- Retrospective analysis of 303 NSCLC patients who underwent EGFR mutation testing between January 2010 and December 2013.
- Measurement of plasma fibrinogen levels prior to treatment.
- Statistical analysis including multivariate analysis and receiver operator characteristic (ROC) curve analysis to assess predictive value.
Main Results:
- Plasma fibrinogen levels were significantly lower in patients with EGFR mutations compared to wild-type EGFR (P<0.001).
- Hyperfibrinogenemia was significantly associated with advanced N and M stages (lymphatic and distant metastasis) (P=0.001 and P=0.025, respectively).
- Multivariate analysis identified fibrinogen (OR 2.5) and smoking status (OR 5.07) as independent predictive factors for EGFR mutation status (AUC=0.75).
Conclusions:
- Plasma fibrinogen is a potential predictive marker for EGFR mutation status in NSCLC, particularly useful when tumor tissue is insufficient.
- Elevated fibrinogen levels correlate with increased metastasis in NSCLC.
- A multivariate model incorporating fibrinogen and smoking history may aid in predicting EGFR mutation status in NSCLC patients.
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