title: Correlation between the Uptake of 18F-Fluorodeoxyglucose (18F-FDG) and the Expression of Proliferation-Associated Antigen Ki-67 in Cancer Patients: A Meta-Analysis.
abstract: OBJECTIVE
  To study the correlation between 18F-FDG uptake and cell proliferation in cancer patients by meta-analysis of published articles.
  
  
  METHODS
  We searched PubMed (MEDLINE included), EMBASE, and Cochrane Database of Systematic Review, and selected research articles on the relationship between 18F-FDG uptake and Ki-67 expression (published between August 1, 1994-August 1, 2014), according to the literature inclusion and exclusion criteria. The publishing language was limited to English. The quality of included articles was evaluated according to the Quality Assessment of Diagnosis Accuracy Studies-2 (QUADAS-2). The correlation coefficient (r) was extracted from the included articles and processed by Fisher's r-to-z transformation. The combined correlation coefficient (r) and the 95% confidence interval (CI) were calculated with STATA 11.0 software under a random-effects model. Begg's test was used to analyze the existence of publication bias and draw funnel plot, and the sources of heterogeneity were explored by sensitivity and subgroup analyses.
  
  
  RESULTS
  According to the inclusion and exclusion criteria, 79 articles were finally included, including 81 studies involving a total of 3242 patients. All the studies had a combined r of 0.44 (95% CI, 0.41-0.46), but with a significant heterogeneity (I2 = 80.9%, P<0.01). Subgroup analysis for different tumor types indicated that most subgroups showed a reduced heterogeneity. Malignant melanoma (n = 1) had the minimum correlation coefficient (-0.22) between 18F-FDG uptake and Ki-67 expression, while the thymic epithelial tumors (TETs; n = 2) showed the maximum correlation coefficient of 0.81. The analytical results confirmed that correlation between 18F-FDG uptake and Ki-67 expression was extremely significant in TETs, significant in gastrointestinal stromal tumors (GISTs), moderate in patients with lung, breast, bone and soft tissue, pancreatic, oral, thoracic, and uterine and ovarian cancers, average in brain, esophageal and colorectal cancers, and poor in head and neck, thyroid, gastric and malignant melanoma tumors. Subgroup analysis indicated that positron emission tomography (PET) or PET/CT imaging technology or Ki-67 and standardized uptake value (SUV) measurement technology did not significantly affect the results of r values, and Begg's test showed no significant publication bias.
  
  
  CONCLUSIONS
  In cancer patients, 18F-FDG uptake showed a moderate positive correlation with tumor cell proliferation. Different tumor types exhibited varied degree of correlation, and the correlation was significant in TETs and GSTs. However, our results need further validation by clinical trials with a large sample of different tumor types.
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China; School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, China.
authors.forename: Sheng-Ming
authors.initials: SM
authors.lastname: Deng
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China; Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Yin-Yin
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Ji-Hui
authors.initials: JH
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Wu
mesh_terms: D001692:Biological Transport; D014408:Biomarkers, Tumor / Q000235:genetics*; D049109:Cell Proliferation; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics*; D009369:Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D009928:Organ Specificity; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000378:metabolism*; D012044:Regression Analysis; D014057:Tomography, X-Ray Computed; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18