Comparative metabolic analysis in head and neck cancer and the normal gingiva
Comparative metabolic analysis in head and neck cancer and the normal gingiva
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DOI：
10.1007/s00784-017-2185-0
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发表时间：
2018-03
影响因子：
3.4
通讯作者：
N. Voelxen;S. Blatt;Pascal Knopf;M. Henkel;Chris Appelhans;L. Righesso;A. Pabst;J. Goldschmitt;S. Walenta;A. Neff;W. Mueller‐Klieser;T. Ziebart
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作者：
N. Voelxen;S. Blatt;Pascal Knopf;M. Henkel;Chris Appelhans;L. Righesso;A. Pabst;J. Goldschmitt;S. Walenta;A. Neff;W. Mueller‐Klieser;T. Ziebart
目的恶性肿瘤组织中乳酸的慢性积累与恶性肿瘤和放射抵抗的增加有关。在这项研究中，对同一患者的原发性头颈部鳞状细胞癌（HNSCC）和正常牙龈的活检进行了代谢谱分析，并与来自无癌患者的健康牙龈进行了比较。材料与方法采用诱导代谢生物发光成像（imBI）技术，对140例HNSCC患者进行龈活检，测定肿瘤和正常牙龈的ATP、乳酸和葡萄糖浓度。此外，对79名健康（无肿瘤）患者的代谢物进行了量化。此外，通过免疫荧光成像和实时荧光定量PCR分析肿瘤样本中乳酸和葡萄糖转运蛋白的表达。结果肿瘤患者、正常牙龈和健康牙龈三种组织中ATP的检测值均有显著性差异。与肿瘤患者的正常牙龈和健康患者的牙龈相比，肿瘤组织中的乳酸浓度显著增加。关于葡萄糖，与肿瘤患者的正常牙龈相比，肿瘤活检中检测到的葡萄糖浓度显著降低。另一方面，患者的肿瘤样本显示，与每位患者相应的正常牙龈相比，单羧酸转运蛋白（MCT-1和MCT-4）以及葡萄糖转运蛋白（GLUT-1和GLUT-3）的相对表达水平显著升高。结论HNSCC中乳酸浓度与原发肿瘤(T)分期相关。临床相关性本研究的目的是确定代谢参数以提高早期癌症诊断，预测恶性程度，并有助于个性化肿瘤治疗。
ObjectivesChronic accumulation of lactate in malignant tumor tissue is associated with increased malignancy and radioresistance. For this study, biopsies of primary head and neck squamous cell carcinoma (HNSCC) and of the normal gingiva of the same patient were compared via metabolic profiling to the healthy gingiva from cancer-free patients.Materials and methodsCryobiopsies of 140 HNSCC patients were used to determine ATP, lactate, and glucose concentrations of the tumor and normal gingiva via induced metabolic bioluminescence imaging (imBI). Additionally, these metabolites were quantified in a collective of 79 healthy (non-tumor-bearing) patients. Furthermore, tumor samples were analyzed via immunofluorescence imaging and quantitative real-time PCR for the expression of lactate and glucose transporters.ResultsThere were significant differences in ATP concentrations detectable between the tumor, normal gingiva of tumor patients, and gingiva from healthy patients. Lactate concentrations were significantly increased in tumor tissue compared to the normal gingiva of tumor patients as well as the gingiva from healthy patients. Concerning glucose, there was a significant decrease in glucose concentrations detectable in the tumor biopsies compared to the normal gingiva of tumor patients. On the other hand, tumor samples from patients revealed significantly elevated relative expression levels of monocarboxylate transporters (MCT-1 and MCT-4), as well as glucose transporters (GLUT-1 and GLUT-3) compared to the corresponding normal gingiva of each patient.ConclusionsWe could demonstrate that the lactate concentration in HNSCC correlates with primary tumor (T) stage.Clinical relevanceThe aim of this study was to identify metabolic parameters to improve early cancer diagnosis, allow predictions on the degree of malignancy, and contribute to a personalized tumor therapy.