title: Relationship between 18F-FDG accumulation and lactate dehydrogenase A expression in lung adenocarcinomas.
abstract: (18)F-FDG PET has been widely used in the management of malignant tumors. Lactate dehydrogenase A (LDHA) plays an important role in the development, invasion, and metastasis of malignancies. However, the relationship between (18)F-FDG accumulation and LDHA expression has not been investigated.
  
  
  METHODS
  Retrospective analysis was conducted for 51 patients with lung adenocarcinomas who underwent (18)F-FDG PET. The relationship between maximum standardized uptake value and the expression of LDHA, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) were examined. RNA interference was used to analyze the role of LDHA in tumor metabolism and growth in A549 cells. The AKT, also known as protein kinase B, pathway was also investigated to evaluate the molecular mechanisms of the relationship between LDHA expression and (18)F-FDG uptake.
  
  
  RESULTS
  Maximum standardized uptake value was significantly higher in the LDHA high-expression group than the LDHA low-expression group (P = 0.018). GLUT1 expression in lung adenocarcinomas was positively correlated with (18)F-FDG accumulation and LDHA expression whereas HK2 expression was not. Knockdown of LDHA led to a significant decrease in GLUT1 expression, (18)F-FDG uptake, and cell proliferation. The activated form of AKT was also decreased after LDHA knockdown.
  
  
  CONCLUSIONS
  LDHA increases (18)F-FDG accumulation into non-small cell lung cancer, possibly by upregulation of GLUT1 expression but not HK2 expression. LDHA may modulate (18)F-FDG uptake in lung adenocarcinomas via the AKT-GLUT1 pathway. These results indicate that (18)F-FDG PET/CT may predict LDHA expression levels and response to anti-LDHA therapy in lung adenocarcinomas.
authors.affiliation: Department of Nuclear Medicine, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Nuclear Medicine, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ruohua
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Nuclear Medicine, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Xie
authors.affiliation: Theragnostic Laboratory, Department of Imaging and Pathology, Faculty of Medicine, KU Leuven, Belgium; and.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Department of Nuclear Medicine, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China huang2802@163.com ljjsh@133sh.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Department of Cancer Metabolism, Institute of Health Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China huang2802@163.com ljjsh@133sh.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D015398:Signal Transduction; D014057:Tomography, X-Ray Computed
chemical_list: D051272:Glucose Transporter Type 1; D007527:Isoenzymes; C495677:SLC2A1 protein, human; D019788:Fluorodeoxyglucose F18; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5
keywords: 18F-FDG uptake; GLUT1; LDHA; glycolysis; lung adenocarcinomas