Association between [18F]-fluoro-2-deoxyglucose uptake and expressions of hypoxia-induced factor 1α and glucose transporter 1 in non-small cell lung cancer

Abstract

Objective: High maximum standardized uptake values on [(18)F]-fluoro-2-deoxyglucose positron emission tomography are associated with inferior survival in non-small cell lung cancer. Here, we investigated the biological mechanisms underlying [(18)F]-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 [(18)F]-fluoro-2-deoxyglucose positron emission tomography. The maximum standardized uptake values for primary lesions were calculated based on [(18)F]-fluoro-2-deoxyglucose uptake. The expression of hypoxia-inducible factor 1α 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 1α 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 1α 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 1α 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 1α and glucose transporter 1, glucose transporter 1 and maximum standardized uptake values, and hypoxia-inducible factor 1α and maximum standardized uptake values were significantly correlated (P < 0.001 for all), suggesting that hypoxia-inducible factor 1α-induced glucose transporter 1 might influence maximum standardized uptake values on [(18)F]-fluoro-2-deoxyglucose positron emission tomography.

Conclusions: In lung adenocarcinoma, but not squamous cell carcinoma, hypoxia-inducible factor 1α and glucose transporter 1 expressions indicate tumour aggressiveness pathologically and might explain high [(18)F]-fluoro-2-deoxyglucose uptake on positron emission tomography and correlate with poor prognosis.

Keywords: [18F]-fluoro-2-deoxyglucose positron emission tomography; glucose transporter 1; hypoxia-inducible factor 1α; non-small cell lung cancer.