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血清游离氨基酸对头颈部癌症的预后意义。

Prognostic Significance of Serum Free Amino Acids in Head and Neck Cancers.

机构信息

Department of Pathological Physiology, Faculty of Medicine, Masaryk University/Kamenice 5, CZ-625 00 Brno, Czech Republic.

Department of Physiology, Faculty of Medicine, Masaryk University/Kamenice 5, CZ-625 00 Brno, Czech Republic.

出版信息

Cells. 2019 May 9;8(5):428. doi: 10.3390/cells8050428.

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.

摘要

尽管在头颈部鳞状细胞癌(HNSCC)生物标志物发现领域取得了显著进展,但具有临床应用价值的预后血清生物标志物的范围仍然有限。由于高度增殖转化细胞的代谢活动与非转化细胞的代谢活动有根本的不同,因此不同代谢物浓度的特定变化可能成为诊断或预后标志物。血液氨基酸已被确定为不同癌症中有前途的生物标志物,但在 HNSCC 领域知之甚少。使用高效液相色谱法检查了 140 例 HNSCC 患者的血液氨基酸谱。Cox 比例风险回归模型用于评估血清中氨基酸浓度的预后价值。集落形成测定用于鉴定在 Cox 比例风险回归模型中具有显著意义的氨基酸对 FaDu 和 Detroit 562 细胞系集落形成能力的影响。在总生存(OS)的多变量 Cox 回归模型中,姑息治疗与不良预后相关,而高血清蛋氨酸水平具有积极的预后影响。在无复发生存(RFS)多变量模型中,蛋氨酸同样被确定为正预后因素,同时口咽部肿瘤定位也是如此。口腔定位和原发性放化疗治疗策略与较差的 RFS 相关。1mM 丝氨酸被证明可支持两种测试的 HNSCC 细胞系形成集落。蛋氨酸的作用则恰恰相反。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99e7/6562773/ca811d82003c/cells-08-00428-g001.jpg

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