Abstract
Despite distinctive advances in the field of head and neck squamous cell cancer (HNSCC) biomarker discovery, the spectrum of clinically useful prognostic serum biomarkers is limited. As metabolic activities in highly proliferative transformed cells are fundamentally different from those in non-transformed cells, specific shifts in concentration of different metabolites may serve as diagnostic or prognostic markers. Blood amino acids have been identified as promising biomarkers in different cancers before, but little is known about this field in HNSCC. Blood amino acid profiles of 140 HNSCC patients were examined using high-performance liquid chromatography. Cox proportional hazards regression model was used to assess the prognostic value of amino acid concentrations in serum. Colony forming assay was used to identify the effect of amino acids that were significant in Cox proportional hazards regression models on colony forming ability of FaDu and Detroit 562 cell lines. In the multivariable Cox regression model for overall survival (OS), palliative treatment was associated with an unfavourable prognosis while high serum levels of methionine have had a positive prognostic impact. In the relapse-free survival (RFS) multivariable model, methionine was similarly identified as a positive prognostic factor, along with tumor localization in the oropharynx. Oral cavity localization and primary radio(chemo)therapy treatment strategy have been linked to poorer RFS. 1mM serine was shown to support the forming of colonies in both tested HNSCC cell lines. Effect of methionine was exactly the opposite.
Highlights
Metabolomics is a relatively new scientific discipline involving the identification and quantification of the small-molecular metabolites produced by an organism under specific conditions
Blood amino acids have been identified as promising biomarkers in different cancers before [8,9,10,11], but little is known about this field in head and neck squamous cell cancer (HNSCC)
Univariate Kaplan-Meier analysis showed a significant positive correlation of high alanine (HR, 0.4846; 95% CI, 0.2928–0.8019, p = 0.00482) and methionine (HR, 0.434; 95% CI, 0.2648–0.7114, p ≥ 0.001) serum levels with overall survival (OS)
Summary
Metabolomics is a relatively new scientific discipline involving the identification and quantification of the small-molecular metabolites produced by an organism under specific conditions. It seems to be a very promising approach for biomarker research due to the dynamic character of the metabolome that reflects current processes in the body. Tumors of the head and neck affect the oral cavity and the upper aerodigestive tract. These tumors most commonly arise from the epithelial layer of mucosal linings. The most frequent histological type of head and neck cancer is squamous cell carcinoma (HNSCC). The prognosis of HNSCC is based on the tumor size and location, the presence of lymph node and distant metastasis
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