Normalized Serum EGF Levels as a Potential Biomarker in Non-Small Cell Lung Cancer: The Role of Platelets

Background: Literature reports contradictory findings regarding the capacity of serum EGF concentrations ([EGF]) to differentiate non-small cell lung cancer (NSCLC) patients from healthy individuals. Therefore, the diagnostic capacity of [EGF], suggestive of dependency on this growth factor in NSCLC patients (tumors) and hence indicative of possible response to therapies directed to EGF/EGFR, is still an open question. Inconsistencies likely derive from the lack of harmonization and standardization in methodologies for blood and sera processing. Methods: A cohort of NSCLC patients was evaluated at diagnosis (25) and after first-line-therapy (18/25). Sera were collected 1 h and 4 h after phlebotomy, controlling the variables influencing [EGF]. EGF was quantified by ELISA. Platelets count was also estimated. The values obtained for several combined and/or normalized by platelets count, variables, were compared to those in selected cohorts of healthy controls. Results: We found differences between healthy individuals and NSCLC patients in the accessibility of EGF to circulation, but not in the total available EGF stock. Indeed, we observed a higher fraction of free EGF in the circulation of patients and consequently a lower amount of EGF stored in platelets. Interestingly, an aberrant relationship between EGF and platelets counts was also observed, especially in patients with thrombocytosis. Moreover, several EGF-related variables, with enough accuracy for discrimination, were identified. Particularly, those variables normalized by platelets count made more evident the differences between patients and healthy controls. Therefore, they might be potential biomarkers in NSCLC. Conclusion: Our results suggest the increase in free/accessible EGF in blood circulation as relevant to the biology of NSCLC, most likely because it reflects a higher accessibility of this growth factor for the tumor. They also suggest some of the study variables to be further evaluated on its predictive value, to select good responders to CIMAvax-EGF® or other therapies targeting the EGF/EGFR system.