Ferritin: A potential serum marker for lymph node metastasis in head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world, yet current treatment options are associated with limited success. The aim of the present study was to investigate the expression of ferritin in HNSCC and clarify whether it may serve as a biomarker for predicting HNSCC metastasis. The chemiluminescent immunoassay method was used to investigate the differences in the serum ferritin (SF) levels between patients with and without tumors, and between HNSCC with and without lymph node metastasis. The iron content and expression levels of ferritin were detected to verify the differences between tumor and normal tissues, and between HNSCC without and with lymph node metastasis. Data from the Gene Expression Omnibus (GEO) dataset was used to support the aforementioned results. No statistically significant difference in the SF level was observed between patients with and without tumors. Iron content and expression levels of ferritin heavy chain (FTH) and ferritin light chain (FTL) were higher in tumor tissues compared with normal tissues. The iron content and expression levels of SF, FTH and FTL were increased in HNSCC with metastasis compared with HNSCC without metastasis. The GEO dataset further verified the results and reported that the expression level of FTH was correlated with the prognosis of patients with HNSCC. Ferritin may not be a biomarker for the early diagnosis of HNSCC. However, an association exists between the expression level of ferritin and HNSCC cervical metastasis. SF may be a potential biomarker for predicting cervical lymph node metastasis in patients with HNSCC.

Altered Iron Metabolism and Impact in Cancer Biology, Metastasis, and Immunology

“…In melanoma samples, high FTL was detected in primary and metastatic lesions by immunohistochemistry but was exclusively cytoplasmic (59). Both FTL and FTH1 stained strongly in head and neck cancer tissues compared to normal and higher expression was observed with metastasis, however further analyses of public data found FTL had no prognostic significance but high FTH1 mRNA predicted poor survival (57). Ovarian cancer samples had elevated FTL and FTH1 detected in the cytoplasm and nucleus compared to benign tissue and increased with tumor grade (60).…”

“…Higher in HNSCC patients with metastasis than without (57). Levels elevated compared to normal controls and associated with poor PFS for neuroblastoma 63…”

Iron: An Essential Element of Cancer Metabolism

“…In the latter, nuclear expression of FTH was shown to prevent iron-derived oxidative DNA damage [200]. Although both FTH and FTL are upregulated in head and neck cancers, only FTH predicted negative prognosis [201,202], whereas the opposite was found in glioblastoma [199]. In melanoma cells, FTL is required to withstand oxidative stress and prevent apoptosis [203].…”

Combined detection of CA15-3, CEA, and SF in serum and tissue of canine mammary gland tumor patients

“…Studies in animal models have illustrated that subcutaneously injected and excess dietary iron increase the possibility of mammary carcinogenesis and accelerated mammary gland tumor progression 15 . It is demonstrated that malignant tumors can synthesize and secrete SF, increasing the amount of SF 16 , 17 . It is reported that human breast cancer are characterized by a higher SF level, when compared with normal tissue 18 .…”