Lactate as a predictive marker for tumor recurrence in patients with head and neck squamous cell carcinoma (HNSCC) post radiation: a prospective study over 15 years
Lactate as a predictive marker for tumor recurrence in patients with head and neck squamous cell carcinoma (HNSCC) post radiation: a prospective study over 15 years
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DOI：
10.1007/s00784-015-1699-6
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发表时间：
2016-11-01
影响因子：
3.4
通讯作者：
Ziebart, Thomas
中科院分区：
文献类型：
--
作者：
Blatt, Sebastian;Voelxen, Nadine;Ziebart, Thomas
n 乳酸作为糖酵解表型的关键调节剂，最近被描述可促进头颈鳞状细胞癌 (HNSCC) 的肿瘤生长和转移扩散。然而，在辅助放疗后肿瘤复发的背景下，其潜在机制仍不确定。因此，我们在这项前瞻性研究中首次在体内研究了乳酸对 HNSCC 放射抗性的作用。在此，我们分析了 17 名患者手术和辅助放射后原发性鳞状细胞癌的活检组织。使用诱导代谢生物发光成像 (imBI) 检测肿瘤组织的 ATP、葡萄糖和乳酸水平，并与长达 15 年观察期内的临床数据相关。HNSCC 肿瘤中的高水平乳酸水平与患者的总体生存率显着负相关。此外，原发肿瘤部位乳酸的高表达与放射后肿瘤复发显着相关，而ATP和/或葡萄糖则没有表现出这种相关性。乳酸不仅可以被视为糖酵解代谢改变的废物产物，而且可以被视为恶性肿瘤以及放射抵抗机制的关键主宰。通过代谢生物发光成像获得的肿瘤组织中乳酸水平的高表达，因此可以作为总体生存和无复发生存的预测因子，并可以代表佐剂验证中的未来生物标志物。辐照。
n Lactate as a key regulator of the glycolytic phenotype has been recently described in fueling tumor growth and metastatic spread in head and neck squamous cell carcinoma (HNSCC). However, in context of tumor recurrence following adjuvant radiation, the underlying mechanisms remain uncertain. We therefore investigate the role of lactate towards radioresistance in HNSCC in this prospective study for the first time in vivo.Herein, we analyzed biopsies of primary squamous cell carcinoma after surgery and adjuvant irradiation in 17 patients. Tumor tissue levels of ATP, glucose, and lactate were detected usig induced metabolic bioluminescence imaging (imBI) and correlated with clinical data within an observation period of up to 15 years.High amounts of lactate levels in tumors of HNSCC are significantly negatively correlated with overall patient survival. Moreover, high expression of lactate in a primary tumor site is significantly correlated with tumor recurrence post radiation, whereas ATP and/or glucose showed no such correlation.Lactate can be seen not only as a waste product of altered glycolytic metabolism but also as a key master of malignancy as well as resistance mechanism towards irradiation.High expression of lactate levels in tumor tissue, obtained by metabolic bioluminescence imaging, may therefore serve as a predictor for overall and recurrence-free survival and could represent a future biomarker in the validation of adjuvant irradiation.