Association between [18F]-fluoro-2-deoxyglucose uptake and expressions of hypoxia-induced factor 1α and glucose transporter 1 in non-small cell lung cancer
Association between [18F]-fluoro-2-deoxyglucose uptake and expressions of hypoxia-induced factor 1α and glucose transporter 1 in non-small cell lung cancer
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DOI：
10.1093/jjco/hyv138
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发表时间：
2015-12-01
影响因子：
2.4
通讯作者：
Okada, Morihito
中科院分区：
文献类型：
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作者：
Furukawa, Takaoki;Miyata, Yoshihiro;Okada, Morihito
目的：[F-18]-氟-2-脱氧葡萄糖正电子发射断层扫描的最大标准化摄取值高与非小细胞肺癌生存率低相关在这里，我们调查的生物学机制[F-18]-氟-2-脱氧葡萄糖摄取在non-small cell lung cancer.Methods：本研究包括133例非小细胞肺癌（109腺癌和24鳞状细胞癌）。患者在[F-18]-氟-2-脱氧葡萄糖正电子发射断层扫描后最迟4周接受肿瘤切除术。根据[F-18]-氟-2-脱氧葡萄糖摄取计算原发性病变的最大标准化摄取值。缺氧诱导因子1 α和葡萄糖转运蛋白1的表达在免疫染色的肿瘤切片上使用六点分级量表进行评估。最大标准化摄取值和低氧诱导因子1 α和葡萄糖转运蛋白1的表达在鳞状细胞癌中显著高于腺癌（P < 0.001，P = 0.034，P < 0.001）。在腺癌中，最大标准化摄取值、缺氧诱导因子1 α和葡萄糖转运蛋白1与恶性肿瘤相关的各种临床病理因素相关，最大标准化摄取值和葡萄糖转运蛋白1与无病生存率相关（P < 0.001和P = 0.029）和总生存期（分别为P < 0.001和P = 0.033）。低氧诱导因子1 α高表达患者的无病生存期和总生存期较低表达患者短，但差异无统计学意义（分别为P = 0.32和P = 0.15）。而在腺癌中，缺氧诱导因子1 α与葡萄糖转运蛋白1、葡萄糖转运蛋白1与最大标准摄取值、缺氧诱导因子1 α与最大标准摄取值均显著相关（P < 0.001），这表明缺氧诱导因子1 α诱导的葡萄糖转运蛋白1可能影响[F-18]-氟-2-结论：在肺腺癌，而不是鳞状细胞癌，缺氧诱导因子1 α和葡萄糖转运蛋白1的表达表明肿瘤的病理侵袭性，并可能解释高[F-18]-氟-2-脱氧葡萄糖摄取的正电子发射断层扫描和预后不良。
Objective: High maximum standardized uptake values on [F-18]-fluoro-2-deoxyglucose positron emission tomography are associated with inferior survival in non-small cell lung cancer. Here, we investigated the biological mechanisms underlying [F-18]-fluoro-2-deoxyglucose uptake in non-small cell lung cancer.Methods: This study included 133 patients with non-small cell lung cancer (109 with adenocarcinoma and 24 with squamous cell carcinoma). The patients underwent tumour resection, at the latest, 4 weeks after [F-18]-fluoro-2-deoxyglucose positron emission tomography. The maximum standardized uptake values for primary lesions were calculated based on [F-18]-fluoro-2-deoxyglucose uptake. The expression of hypoxia-inducible factor 1 alpha and glucose transporter 1 was evaluated on immunostained tumour sections using six-point grading scales.Results: Maximum standardized uptake values and the expression of hypoxia-inducible factor 1 alpha and glucose transporter 1 were significantly higher in squamous cell carcinoma than in adenocarcinoma (P < 0.001, P = 0.034 and P < 0.001, respectively). In adenocarcinoma, but not squamous cell carcinoma, maximum standardized uptake values, hypoxia-inducible factor 1 alpha and glucose transporter 1 correlated with various clinicopathological factors relating to malignancy, and maximum standardized uptake values and glucose transporter 1 were associated with disease-free survival (P < 0.001 and P = 0.029) and overall survival (P < 0.001 and P = 0.033, respectively). Patients with high expression of hypoxia-inducible factor 1 alpha tended to exhibit shorter disease-free survival and overall survival than those with low expression, but the differences were not significant (P = 0.32 and P = 0.15, respectively). And then in adenocarcinoma, hypoxia-inducible factor 1 alpha and glucose transporter 1, glucose transporter 1 and maximum standardized uptake values, and hypoxia-inducible factor 1 alpha and maximum standardized uptake values were significantly correlated (P < 0.001 for all), suggesting that hypoxia-inducible factor 1 alpha-induced glucose transporter 1 might influence maximum standardized uptake values on [F-18]-fluoro-2-deoxyglucose positron emission tomography.Conclusions: In lung adenocarcinoma, but not squamous cell carcinoma, hypoxia-inducible factor 1 alpha and glucose transporter 1 expressions indicate tumour aggressiveness pathologically and might explain high [F-18]-fluoro-2-deoxyglucose uptake on positron emission tomography and correlate with poor prognosis.