The hunt for biomarkers

Cancer patients and physicians often face the question, “Will this treatment benefit this individual patient?” Scientists prefer to answer this question by measuring a biomarker in the blood, urine or tumor tissue from the patient.

Biomarkers: what, when, and why

As a review, all cancers express some molecules differently than normal cells. A biomarker usually is a molecule that is found only in patients with a specific disease, such as lung cancer or mesothelioma. Alternatively, a biomarker can be the loss of a specific molecule found in normal cells or it may be a mutated protein. While some biomarkers are found only on the tissue, biomarkers are easier to monitor if they can be measured in the blood or urine of a patient. Some biomarkers help identify people with early cancer. Other biomarkers help predict which group of patients can benefit the most from a specific treatment.

Fibrinogen: a potential biomarker for lung cancer

In honor of May being Cancer Research Month, we’ll describe the promising role of fibrinogen as a biomarker. Fibrinogen is a large protein coated with sugars (glycoprotein, 340kDa) in the blood. During an injury, fibrinogen is cleaved by clotting factors to make fibrin. Fibrin is laid down over the wound and forms an essential part of the clot. The advantage of fibrinogen as a marker is that the patients’ fibrinogen levels are routinely taken before treatment. Abnormal fibrinogen levels can suggest a clotting disorder or an acute infection: important information for the treating physicians.

Some non-small cell lung cancer (NSCLC) patients have high levels of fibrinogen (>4400 mg/L) in their blood before therapy. The fibrinogen levels were monitored in all patients with lung cancer in the study1. Patients with high fibrinogen (hyperfibrinogenemia) had a higher risk of their tumor growing rapidly and death1, 2. After chemotherapy, the fibrinogen levels declined in 61% of patients (who originally had high levels of it). Zhao suggests, “reduction of plasma fibrinogen levels is as promising a biomarker as CEA and CA125“ to monitor the effectiveness of chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Research continues on developing fibrinogen as a biomarker for monitoring cancer progression and response of lung cancer to treatment.

Fibrinogen: potential biomarker for response to multimodality therapy of mesothelioma

Fibrinogen also is potentially a useful biomarker in patients with mesothelioma. Most patients with mesothelioma have higher levels of fibrinogen than normal patients (150 mg/dL to 300 mg/dL). In Ghanim et al.’s retrospective study3, mesothelioma patients with fibrinogen levels less than 627 mg/dL had significantly longer survival times compared to mesothelioma patients with fibrinogen levels at 628mg/dL or greater. Some patients received surgery, chemotherapy and radiotherapy whereas other patients chose chemotherapy and radiotherapy but no surgery.

Multivariate analysis calculated which variables were associated with longer survival. The authors chose to regroup the patients based on the fibrinogen level found in 75% of mesothelioma patients (at or less than 750mg/dL). Ghanim et al3 found that the group of mesothelioma patients with fibrinogen levels at 750 mg/dL or below showed significantly longer survival (median of 31 months) if they received all three treatments— surgery, chemotherapy, and radiation than those who only received chemotherapy and radiotherapy (13.8 month). In contrast, the group of patients with fibrinogen levels above 750 mg/dL did not benefit from the surgery and had a median overall survival of 5.1 months. In this study, the fibrinogen level of 750 mg/dL had a sensitivity of 31.3% and a specificity of 82.9%.

The use of fibrinogen as a predictor of overall survival or response to the multimodality therapy (surgery, chemotherapy and radiation) in mesothelioma patients is under development.