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Serum amino acids, head and neck squamous cell cancers prognosis and correlation with in-vitro conditions

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KALFERT David GUMULEC Jaromír MASAŘÍK Michal VŠIANSKÝ Vít PLZÁK Jan SMILEK Pavel RAUDENSKÁ Martina

Rok publikování 2021
Druh Konferenční abstrakty
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Popis Introduction: Head and neck squamous cell carcinoma (HNSCC) represent an aggressive tumor with unfavorable prognosis, with many cases of recurrent disease. Despite distinctive advances in the field of HNSCC biomarker discovery, no clinically useful prognostic serum biomarkers have been found yet for HNSCC. The aim of the present studywas to investigate amino acids in relation to overall survival (OS) and to relapse-free survival (RFS) of patients with HNSCC. Materials and Methods: Blood sampleswere taken from 140 patients with histologically verified primary HNSCC. The blood samples were centrifuged at 3000 rpm at 4°C for 10 min within 60 min after collection. The serumwas aliquoted and stored at -80°C until analysis. The determination of amino acids was performed by high-performance liquid chromatography with fluorescence detection. Patients were split into groups with high or low various amino acid concentrations in serum based on cut-off points calculated by maximally selected rank statistics. Univariable, as well as multivariable Cox proportional hazards regression models, were used to assess the prognostic value of amino acid concentrations in serum as well as clinicopathologic features. For in vitro experiment were used two cell lines (FaDu and Detroit 562). Colony forming assay was performed in cell seeding density 100–2000 cells/well. Results: In the multivariate Cox regression model for OS and RFS, high methionine serum levels turned out to be a significant positive prognostic factor with HR = 0.5248 (95% CI = 0.3056–0.9013), p = 0.0195 and HR = 0.4373 (95% CI 0.19240–0.9941), p = 0.04836 for OS and RFS, respectively. On the other hand, no studied amino acid was found to be a significant negative prognostic factor for OS or RFS in this model. It was found out that the in vitro experiment is in accordance with overall survival: methionine, which was associated with better patient prognosis, inhibited the growth of cells (4% and 3% growth decrease at p = 0.05 and 0.04 for FaDu and Detroit 562, resp.). On the other hand, serine in the same non-toxic concentration (1 mM) demonstrated support of tumor cell line growth (4% and 6% growth increase at p = 0.05 and <0.001 for FaDu and Detroit 562, resp.). Conclusions: The preliminary results of our study suggest that serum amino acids (mainly methionine) may be possibility prognostic biomarker with a clear biological background in patients with HNSCC.

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