MedWire News: Gene expression profiling has identified fibronectin 1 and chemokine ligand (CXCL)9 as candidate biomarkers for breast cancer screening, French researchers report.
“Until now, no serum biomarker has been shown to allow an early diagnosis of breast cancer,” say Fabrice Andre (Institut Gustave Roussy, Villejuif) and colleagues.
In the present study, Andre and team used a gene expression data set that included 120 breast cancer samples and 45 benign lesions to identify protein-encoding genes that are overexpressed in breast cancer compared with the benign lesions.
Two proteins, fibronectin 1 and CXCL9, were identified as candidate biomarkers for blood-based screening. They both had more than two-fold increased expression in the cancer compared with the benign lesion, were proteins that are released in the extracellular medium and stable in serum, and had a commercially available and accurate enzyme-linked immunosorbent assay (ELISA).
To evaluate the potential of these proteins as biomarkers for breast cancer, the researchers tested blood samples from 113 patients with early breast cancer and 119 healthy controls.
They found that patients had significantly higher CXCL9 and fibronectin 1 concentrations than controls. The mean CXCL9 concentration was 851 pg/ml in patients compared with 635pg/ml in controls. For fibronectin, the mean concentration was 190 µg/ml in patients and 125 µg/ml in the controls.
Receiver operating characteristic analysis revealed an area under the curve for breast cancer diagnosis of 0.78 for fibronectin 1 (cut-off 150 pg/ml) and 0.62 for CXCL9 (cut-off 1000 pg/ml).
An assay combining Fibronectin 1 and CXCL9 had a sensitivity of 53%, a specificity of 98% and a positive predictive value of 96% for breast cancer, report the researchers in the British Journal of Cancer.
Of note, similar results were observed when the team only considered estrogen receptor-negative tumors (34.5% of total).
Andre and co-authors comment that an assay used in conjunction with mammogram should have high specificity to avoid any additional false-positive results and unnecessary biopsies.
They conclude: “Differential gene expression analysis is a good approach to select candidate biomarkers to set up blood assays cancer screening.”
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