Application of Differential Expression of Genetic Profiles in Brain Tumors with Variable [$^{18}F$]-fluorodeoxyglucose Uptake

  • Lee, Seung-Ho (Department of Biochemistry & Molecular Biology, College of Medicine, Korea University) ;
  • Yun, Mi-Jin (Department of Biochemistry & Molecular Biology, College of Medicine, Korea University) ;
  • Kim, Ki-Nam (Department of Biochemistry & Molecular Biology, College of Medicine, Korea University) ;
  • Seo, Sang-Hui (Department of Biochemistry & Molecular Biology, College of Medicine, Korea University) ;
  • Sohn, Sung-Hwa (Department of Biochemistry & Molecular Biology, College of Medicine, Korea University) ;
  • Kim, Yu-Ri (Department of Biochemistry & Molecular Biology, College of Medicine, Korea University) ;
  • Kim, Hye-Won (Department of Biochemistry & Molecular Biology, College of Medicine, Korea University) ;
  • Kim, In-Kyoung (Department of Biochemistry & Molecular Biology, College of Medicine, Korea University) ;
  • Shim, Boo-Im (Department of Biochemistry & Molecular Biology, College of Medicine, Korea University) ;
  • Lee, Seung-Min (Department of Biochemistry & Molecular Biology, College of Medicine, Korea University) ;
  • Kim, Meyoung-Kon (Department of Biochemistry & Molecular Biology, College of Medicine, Korea University)
  • Published : 2007.09.30

Abstract

[ $^{18}F$ ]-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumor aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of glial tumors were evaluated to determine whether glial tumors with high $^{18}F$-FDG uptake have more aggressive biological potential than with low uptake. Surgical specimens were obtained from the 12 patients with glial tumors (4 males and 8 females, age range 42-68 years). The tumor samples were divided into two groups based on the $^{18}F$-FDG uptake PET scan findings: high $^{18}F$-FDG uptake (n=4) and low $^{18}F$-FDG uptake (n=8). The pathological tumor grade was closely correlated with the $^{18}F$-FDG uptake pattern: Glial tumors with high $^{18}F$-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were grade II. The total RNA was extracted from the frozen tissues of all glial tumors (n=12), and adjacent non-cancerous tissue (n=3). The gene expression profiles were evaluated using cDNA microarray. The glial tumors with high $^{18}F$-FDG uptake showed increase expression of 15 genes compared to those with low uptake (P<0.005). Nine genes were down-regulated. Gene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, glial tumors with high $^{18}F$-FDG uptake appear to have more aggressive biological properties than those with low uptake.

Keywords

References

  1. Silvestri, L. et al. CYP enzyme polymorphisms and susceptibility to HCV-related chronic liver disease and liver cancer. Int J Cancer 104:310-317 (2003) https://doi.org/10.1002/ijc.10937
  2. Di Chiro, G. et al. Issues in the in vivo measurement of glucose metabolism of human central nervous system tumors. Ann Neurol 15:S138-146 (1984) https://doi.org/10.1002/ana.410150727
  3. Hagge, R. J., Wong, T. Z., & Coleman, R. E. Positron emission tomography: brain tumors and lung cancer. Radiol Clin North Am 39:871-881 (2001) https://doi.org/10.1016/S0033-8389(05)70318-3
  4. Kim, C. K., Alavi, J. B., Alavi, A. & Reivich, M. New grading system of cerebral gliomas using positron emission tomography with F-18 fluorodeoxyglucose. J Neurooncol 10:85-91 (1991) https://doi.org/10.1007/BF00151249
  5. Delbeke, D. et al. Optimal cutoff levels of F-18 fluorodeoxyglucose uptake in the differentiation of lowgrade from high-grade brain tumors with PET. Radiology 195:47-52 (1995) https://doi.org/10.1148/radiology.195.1.7892494
  6. De Witte, O. et al. Prognostic value positron emission tomography with [$^{18}F]fluoro-2-deoxy-D-glucose in the low-grade glioma. Neurosurgery 39:470-476; discussion 476-477 (1996) https://doi.org/10.1097/00006123-199609000-00007
  7. Barker, F. G. et al. 18-Fluorodeoxyglucose uptake and survival of patients with suspected recurrent malignant glioma. Cancer 79:115-126 (1997) https://doi.org/10.1002/(SICI)1097-0142(19970101)79:1<115::AID-CNCR17>3.0.CO;2-7
  8. Schifter, T. et al. Serial FDG-PET studies in the prediction of survival in patients with primary brain tumors. J Comput Assist Tomogr 17:509-561 (1993)
  9. Chao, S. T. et al. The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery. Int J Cancer 96:191-197 (2001) https://doi.org/10.1002/ijc.1016
  10. Vansteenkiste, J. F. et al. Prognostic importance of the standardized uptake value on (18)F-fluoro-2- deoxy-glucose-positron emission tomography scan in non-small-cell lung cancer: An analysis of 125 cases. Leuven Lung Cancer Group. J Clin Oncol 17:3201-3206 (1999) https://doi.org/10.1200/JCO.1999.17.10.3201
  11. Halfpenny, W. et al. A possible prognostic factor in head and neck cancer. Br J Cancer 86:512-516 (2002) https://doi.org/10.1038/sj.bjc.6600114
  12. Spaepen, K. et al. Prognostic value of pretransplantation positron emission tomography using fluorine 18- fluorodeoxyglucose in patients with aggressive lymphoma treated with high-dose chemotherapy and stem cell transplantation. Blood 102:53-59 (2003) https://doi.org/10.1182/blood-2002-12-3842
  13. Nakata, B. et al. $^{18}F-fluorodeoxyglucose positron emission tomography and the prognosis of patients with pancreatic adenocarcinoma. Cancer 79:695-699 (1997) https://doi.org/10.1002/(SICI)1097-0142(19970215)79:4<695::AID-CNCR6>3.0.CO;2-D
  14. Burt, B. M. et al. Using positron emission tomography with [(18)F]FDG to predict tumor behavior in experimental colorectal cancer. Neoplasia 3:189-195 (2001) https://doi.org/10.1038/sj.neo.7900147
  15. Miller, T. R., Pinkus, E., Dehdashti, F. & Grigsby, P. W. Improved prognostic value of $^{18}F-FDG PET using a simple visual analysis of tumor characteristics in patients with cervical cancer. J Nucl Med 44:192-197 (2003)
  16. Downey, R. J. et al. Whole body 18FDG-PET and the response of esophageal cancer to induction therapy: results of a prospective trial. J Clin Oncol 21:428-432 (2003) https://doi.org/10.1200/JCO.2003.04.013
  17. Chung, J. K., et al. Comparison of [$^{18}F]fluorodeoxyglucose uptake with glucose transporter-1 expression and proliferation rate in human glioma and non-small-cell lung cancer. Nucl Med Commun 25:11-17 (2004) https://doi.org/10.1097/00006231-200401000-00003
  18. Meyer, P. T. et al. High F-18 FDG uptake in a lowgrade supratentorial ganglioma: a positron emission tomography case report. Clin Nucl Med 25:694-697 (2000) https://doi.org/10.1097/00003072-200009000-00008
  19. Lee, J. K., Liu, R. S., Shiang, H. R. & Pan, D. H. Usefulness of semiquantitative FDG-PET in the prediction of brain tumor treatment response to gamma knife radiosurgery. J Comput Assist Tomogr 27:525-529 (2003) https://doi.org/10.1097/00004728-200307000-00012
  20. Wong, T. Z., van der Westhuizen, G. J. & Coleman, R. E. Positron emission tomography imaging of brain tumors. Neuroimaging Clin N Am 12:615-626 (2002) https://doi.org/10.1016/S1052-5149(02)00033-3
  21. Hoffman, J. M. et al. FDG-PET in pediatric posterior fossa brain tumors. J Comput Assist Tomogr 16:62-68 (1992) https://doi.org/10.1097/00004728-199201000-00011
  22. Meyer, P. T. et al. Comparison of visual and ROIbased brain tumour grading using $^{18}F-FDG PET: ROC analyses. Eur J Nucl Med 28:165-174 (2001) https://doi.org/10.1007/s002590000428
  23. Vesselle, H. et al. Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res 6:3837-3844 (2000)
  24. Higashi, K., Clavo, A. C. & Wahl, R. L. Does FDG uptake measure proliferative activity of human cancer cells? In vitro comparison with DNA flow cytometry and tritiated thymidine uptake. J Nucl Med 34:414-419 (1993)
  25. Chen, C. C. Protein kinase C alpha, delta, epsilon and zeta in C6 glioma cells. TPA induces translocation and down-regulation of conventional and new PKC isoforms but not atypical PKC zeta. FEBS Lett 332: 169-173 (1993) https://doi.org/10.1016/0014-5793(93)80506-P
  26. Bredel, M. et al. Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas. Cancer Res 65:8679-8689 (2005) https://doi.org/10.1158/0008-5472.CAN-05-1204
  27. Mischel, P. S., Cloughesy, T. F. & Nelson, S. F. DNA-microarray analysis of brain cancer: molecular classification for therapy. Nat Rev Neurosci 5:782-792 (2004) https://doi.org/10.1038/nrn1518
  28. Sallinen, S. L. et al. Identification of differentially expressed genes in human gliomas by DNA microarray and tissue chip techniques. Cancer Res 60: 6617-6622 (2000)
  29. Fuller, G. N. et al. Reactivation of insulin-like growth factor binding protein 2 expression in glioblastoma multiforme: a revelation by parallel gene expression profiling. Cancer Res 59:4228-4232 (1999)
  30. Hoelzinger, D. B. et al. Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets. Neoplasia 7:7-16 (2005) https://doi.org/10.1593/neo.04535
  31. Glick, R. P., Unterman, T. G., Van der Woude, M. & Blaydes, L. Z. Insulin and insulin-like growth factors in central nervous system tumors. Part V: Production of insulin-like growth factors I and II in vitro. J Neurosurg 77:445-450 (1992) https://doi.org/10.3171/jns.1992.77.3.0445
  32. Sandberg-Nordqvist, A. C. et al. Characterization of insulin-like growth factor 1 in human primary brain tumors. Cancer Res 53:2475-2478 (1993)
  33. Morford, L. A., Boghaert, E. R., Brooks, W. H. & Roszman, T. L. Insulin-like growth factors (IGF) enhance three-dimensional (3D) growth of human glioblastomas. Cancer Lett 115:81-90 (1997) https://doi.org/10.1016/S0304-3835(97)04717-4
  34. Jones, J. I. & Clemmons, D. R. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16:3-34 (1995)
  35. Ranke, M. B. & Elmlinger, M. Functional role of insulin- like growth factor binding proteins. Horm Res 48(4): 9-15 (1997) https://doi.org/10.1159/000191304
  36. Zapf, J. Physiological role of the insulin-like growth factor binding proteins. Eur J Endocrinol 132:645-654 (1995) https://doi.org/10.1530/eje.0.1320645
  37. Blum, W. F. et al. Insulin-like growth factor I (IGFI)- binding protein complex is a better mitogen than free IGF-I. Endocrinology 125:766-772 (1989) https://doi.org/10.1210/endo-125-2-766
  38. Cerro, J. A., Grewal, A., Wood, T. L. & Pintar, J. E. Tissue-specific expression of the insulin-like growth factor binding protein (IGFBP) mRNAs in mouse and rat development. Regul Pept 48:189-198 (1993) https://doi.org/10.1016/0167-0115(93)90347-B
  39. Wood, T. L., Streck, R. D. & Pintar, J. E. Expression of the IGFBP-2 gene in post-implantation rat embryos. Development 114:59-66 (1992)
  40. Ho, P. J. & Baxter, R. C. Insulin-like growth factorbinding protein-2 in patients with prostate carcinoma and benign prostatic hyperplasia. Clin Endocrinol (Oxf) 46:333-342 (1997)
  41. Menouny, M., Binoux, M. & Babajko, S. IGFBP-2 expression in a human cell line is associated with increased IGFBP-3 proteolysis, decreased IGFBP-1 expression and increased tumorigenicity. Int J Cancer 77:874-879 (1998) https://doi.org/10.1002/(SICI)1097-0215(19980911)77:6<874::AID-IJC13>3.0.CO;2-1
  42. Eberhart, C. E. et al. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107:1183-1188 (1994) https://doi.org/10.1016/0016-5085(94)90246-1
  43. Kutchera, W. et al. Prostaglandin H synthase 2 is expressed abnormally in human colon cancer: evidence for a transcriptional effect. Proc Natl Acad Sci USA 93:4816-4820 (1996)
  44. Sano, H. et al. Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res 55:3785-3789 (1995)
  45. Smalley, W. E. & DuBois, R. N. Colorectal cancer and nonsteroidal anti-inflammatory drugs. Adv Pharmacol 39:1-20 (1997) https://doi.org/10.1016/S1054-3589(08)60067-8
  46. Hida, T. et al. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res 58:3761-3764 (1998)
  47. Tucker, O. N. et al. Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res 59:987-990 (1999)
  48. Sheng, G. G. et al. A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras-transformed rat intestinal epithelial cells. Gastroenterology 113: 1883-1891 (1997) https://doi.org/10.1016/S0016-5085(97)70007-6
  49. Subbaramaiah, K. et al. Transcription of cyclooxygenase- 2 is enhanced in transformed mammary epithelial cells. Cancer Res 56:4424-4429 (1996)
  50. Zhang, X., Morham, S. G., Langenbach, R. & Young, D. A. Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase-null embryo fibroblasts. J Exp Med 190:451-459 (1999) https://doi.org/10.1084/jem.190.4.451
  51. Butti, G. et al. A study on the biological behavior of human brain tumors. Part II: Steroid receptors and arachidonic acid metabolism. J Neurooncol 10:241-246 (1991)
  52. Pai, R. et al. Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med 8:289-293 (2002) https://doi.org/10.1038/nm0302-289
  53. Buchanan, F. G., Wang, D., Bargiacchi, F. & DuBois, R. N. Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal growth factor receptor. J Biol Chem 278:35451-35457 (2003) https://doi.org/10.1074/jbc.M302474200
  54. Vawter, M. P. et al. Application of cDNA microarrays to examine gene expression differences in schizophrenia. Brain Res Bull 55:641-650 (2001) https://doi.org/10.1016/S0361-9230(01)00522-6
  55. Tanaka, T. S. et al. Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. Proc Natl Acad Sci 97:9127-9132 (2000)
  56. Eisen M. B., Spellman P. T., Brown P. O. & Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci 95:14863-14868 (1998)