The Utility of Circulating EGFR, EGF, and TGF-α as Biomarkers for Fluorescence Imaging in Head and Neck Cancer Tissues

Abstract Purpose EGFR (Epidermal growth factor receptor) is a prominent oncogene in HNSCC (Head and neck squamous cell carcinoma) and a major target for fluorescence-guided surgery (FGS). Soluble fragments of the EGFR axis including the extracellular domain fragment (sEGFR) and ligands EGF and TGF-α are detectable in serum, but their role as predictive biomarkers for fluorescence imaging remains unclear. This study determines whether circulating EGFR-axis biomarkers can stratify HNSCC patients suitable for EGFR-targeted FGS. Procedures Serum collected prior to antibody infusion from 47 HNSCC patients (including 27 patients who received panitumumab-IRDye800CW (PAN800) and 20 patients who did not receive PAN800) and 20 healthy controls was analyzed for various markers using ELISA. Tissue EGFR expression was assessed by IHC, and fluorescence metrics, mean fluorescence intensity (MFI) and tumor-to-background ratio (TBR) were quantified in resected specimens. Results sEGFR, sEGF, and TGF-α were significantly lower in HNSCC patients than healthy controls. Circulating biomarkers did not significantly influence tumor MFI. However, sEGFR showed a significant non-linear association with TBR (adjusted R 2 = 0.66, Spearman ρ = − 0.76; both p < 0.001). Tissue EGFR expression significantly predicted MFI (ρ = 0.52, p = 0.011) and TBR (ρ = 0.443, p = 0.034). ROC analysis identified sEGFR as an excellent preoperative predictor of adequate imaging contrast (TBR ≥ 2; AUC = 0.94, cutoff 23.3 ng/mL, sensitivity 100%, specificity 80%), with a composite sEGFR + sEGF model achieving AUC = 0.989 (sensitivity 94.4%, specificity 100%). Conclusions Soluble EGFR-axis components are biologically relevant, clinically accessible biomarkers that can stratify patient suitability for EGFR-targeted FGS. Trial registration ClinicalTrials.gov identifier: NCT04511078, Study start:12/08/2020, https://clinicaltrials.gov/study/NCT04511078?cond=NCT04511078%20&rank=1