Serum Ferritin Fuctions As Biomarker Of Regional Metastasis Of Head And Neck Squamous Cell Carcinoma

Purpose:Regional neck lymph node metastasis is an important prognostic factor of Head and Neck Squamous Cell Carcinoma (HNSCC). The sensitivity of Ultrasound (US) for detecting metastasis was not totally reliable in clinical practice. The aim of this study was to investigate a new biomarker (serum ferritin) for predicting metastasis of HNSCC.Experimental Design:Seventy patients with HNSCC who all had performed neck dissection were retrospectively analyzed. Size (longitudinal diameter×axial diameter) and shape (long axis/short axis or L/S Ratio) of the largest lymph node of each patient were assayed by US. Serum ferritin of each patient was tested using enhanced chemiluminescence. Correlation between US or serum ferritin and lymph node metastasis were analyzed. Then, the Cancer Genome Atlas project (TCGA) was used to analyze the correlation between ferritin gene expression and suvival of patients with HNSCC. We next analyzed the expression of ferritin in primary tumor and lymph node using immunohistochemistry. The iron content in tissues was also investigated by prussion staining. Finally, correlation analysis was done to analyze the correlation between serum ferritin and ferritin or iron in tissue.Result:The positive rate of neck dissection was 42.9%. For US, the sensitivity and specificity of longitudinal diameter and L/S ratio for detecting metastasis was 60%, 20% and 37.5%,10%, respectively. The difference between the longitudinal diameter or L/S ratio and metastasis had no statistical significance (P>0.05). The sensitivity and specificity of serum ferritin for detecting metastasis was 86.7%,77.5%, respectively. The serum ferritin level had marked statistical significance for detecting neck metastasis (P<0.01). Ferritin gene expression correlated tightly with suvival of patients with HCSCC. Ferritin and iron expression in primary tumor and lymph node with metastasis was higher than that with non-metastasis.Conclusion:The positive rate of neck dissection in clinic was low. US was not totally reliable for detecting regional lymph node metastasis. Serum ferritin level could be acted as a new and effective serum biomarker of metastasis of HNSCC.