title: 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.
authors.affiliation: Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima.
authors.forename: Takaoki
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyata
authors.affiliation: Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kushitani
authors.affiliation: Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mimae
authors.affiliation: Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsutani
authors.affiliation: Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Takeshima
authors.affiliation: Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima morihito1217@gmail.com.
authors.forename: Morihito
authors.initials: M
authors.lastname: Okada
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011013:Pneumonectomy; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000378:metabolism*
chemical_list: D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: [18F]-fluoro-2-deoxyglucose positron emission tomography; glucose transporter 1; hypoxia-inducible factor 1α; non-small cell lung cancer