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VEGF-A and its isoform VEGF121 mRNA expression measured by quantitative real-time RT-PCR: correlation with F-18 FDG uptake and aggressiveness of lung adenocarcinoma: preliminary study

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Abstract

Objective

To investigate the correlation of vascular endothelial growth factor (VEGF) A and its isoform VEGF 121 mRNA expression with F-18 fluorodeoxyglucose (FDG) uptake and aggressiveness in lung adenocarcinoma.

Methods

Twenty-three patients with lung adenocarcinoma underwent FDG PET before surgery. As semi-quantitative analysis for FDG uptake, partial volume corrected standardized uptake value (PVC-SUV) of the tumor was calculated. Total RNA from lung adenocarcinoma tissue was prepared from the frozen specimens. Using the real-time reverse transcription polymerase chain reaction method, we analyzed the mRNA level of VEGF-A and VEGF-A isoform VEGF121 mRNA level. 18S ribosomal RNA was used as an endogenous control.

Results

VEGF-A and VEGF121 mRNA levels had significantly positive correlation with PVC-SUV in lung adenocarcinoma (r = 0.477, p = 0.021, r = 0.539, p = 0.008, respectively), while they were not correlated with tumor size (≤3 or >3 cm). VEGF-A and VEGF121 mRNA levels of the low FDG uptake group were significantly lower than those of the high FDG uptake group (p = 0.005 and p = 0.004, respectively). FDG uptake (PCV-SUV) of aggressive lung adenocarcinoma was higher than that of non-aggressive lung adenocarcinoma (p = 0.01). VEGF-A and VEGF121 mRNA levels of aggressive lung adenocarcinoma were higher than those of non-aggressive lung adenocarcinoma (p = 0.0001 and p = 0.0001, respectively).

Conclusion

VEGF-A and VEGF121 mRNA levels may correlate with FDG uptake and aggressiveness in lung adenocarcinoma. These findings support the hypothesis that VEGF-A and VEGF121 may help in predicting the outcome in patients with lung adenocarcinoma.

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References

  1. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1:27–31.

    Article  CAS  PubMed  Google Scholar 

  2. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989;246:1306–9.

    Article  CAS  PubMed  Google Scholar 

  3. Fontanini G, Vignati S, Boldrini L, Chine S, Silvestri V, Lucchi M, et al. Vascular endothelial growth factor is associated with neovascularization and influences progression of non-small cell lung carcinoma. Clin Cancer Res. 1997;3:861–5.

    CAS  PubMed  Google Scholar 

  4. Imoto H, Osaki T, Taga S, Ohgami A, Ichiyoshi Y, Yasumoto K. Vascular endothelial growth factor expression in non-small-cell lung cancer: prognostic significance in squamous cell carcinoma. J Thorac Cardiovasc Surg. 1998;115:1007–14.

    Article  CAS  PubMed  Google Scholar 

  5. Ohta Y, Watanabe Y, Murakami S, Oda M, Hayashi Y, Nonomura A, et al. Vascular endothelial growth factor and lymph node metastasis in primary lung cancer. Br J Cancer. 1997;76:1041–5.

    CAS  PubMed  Google Scholar 

  6. Ohta Y, Endo Y, Tanaka M, Shimizu J, Oda M, Hayashi Y, et al. Significance of vascular endothelial growth factor messenger RNA expression in primary lung cancer. Clin Cancer Res. 1996;2:1411–6.

    CAS  PubMed  Google Scholar 

  7. Higashi K, Ito K, Hiramatsu Y, Ishikawa T, Sakuma T, Matsunari I, et al. 18F-FDG uptake by primary tumor as a predictor of intratumoral lymphatic vessel invasion and lymph node involvement in non-small cell lung cancer: analysis of a multicenter study. J Nucl Med. 2005;46:267–73.

    PubMed  Google Scholar 

  8. Okada M, Tauchi S, Iwanaga K, Mimura T, Kitamura Y, Watanabe H, et al. Associations among bronchioloalveolar carcinoma components, positron emission tomographic and computed tomographic findings, and malignant behavior in small lung adenocarcinomas. J Thorac Cardiovasc Surg. 2007;133:1448–54.

    Article  PubMed  Google Scholar 

  9. Nomori H, Watanabe K, Ohtsuka T, Naruke T, Suemasu K, Kobayashi T, et al. Fluorine 18-tagged fluorodeoxyglucose positron emission tomographic scanning to predict lymph node metastasis, invasiveness, or both, in clinical T1 N0 M0 lung adenocarcinoma. J Thorac Cardiovasc Surg. 2004;128:396–401.

    Article  PubMed  Google Scholar 

  10. Vansteenkiste J, Fischer BM, Dooms C, Mortensen J. Positron-emission tomography in prognostic and therapeutic assessment of lung cancer: systemic review. Lancet Oncol. 2004;5:531–40.

    Article  PubMed  Google Scholar 

  11. Hanin FX, Lonneux M, Cornet J, Noirhomme P, Coulon C, Distexhe J, et al. Prognostic value of FDG uptake in early stage non-small cell lung cancer. Eur J Cardiothorac Surg. 2008;33:819–23.

    Article  PubMed  Google Scholar 

  12. Sasaki R, Komaki R, Macapinlac H, Erasmus J, Allen P, Forster K, et al. [18F]fluorodeoxyglucose uptake by positron emission tomography predicts outcome of non-small-cell lung cancer. J Clin Oncol. 2005;23:1136–43.

    Article  CAS  PubMed  Google Scholar 

  13. Strauss LG, Koczan D, Klippel S, Pan L, Cheng C, Willis S, et al. Impact of angiogenesis-related gene expression on the tracer kinetics of 18F-FDG in colorectal tumors. J Nucl Med. 2008;49:1238–44.

    Article  CAS  PubMed  Google Scholar 

  14. Kaira K, Oriuchi N, Shimizu K, Ishikita T, Higuchi T, Imai H, et al. Correlation of angiogenesis with (18)F-FMT and (18)F-FDG uptake in non-small cell lung cancer. Cancer Sci. 2009;100:753–8.

    Article  CAS  PubMed  Google Scholar 

  15. Guo J, Higashi K, Ueda Y, Kodama Y, Oguchi M, Taki S, et al. Microvessel density: correlation with FDG uptake and prognostic impact in lung adenocarcinomas. J Nucl Med. 2006;47:419–25.

    CAS  PubMed  Google Scholar 

  16. Kanno I, Iida H, Miura S, Yamamoto S, Amano M, Hirose Y, et al. Design concepts and preliminary performances of stationary-sampling whole-body high-resolution positron emission tomography: HEADTOME IV. Kaku Igaku. 1989;26:477–85.

    CAS  PubMed  Google Scholar 

  17. Guo J, Higashi K, Yokota H, Nagao Y, Ueda Y, Kodama Y, et al. In vitro proton magnetic resonance spectroscopic lactate and choline measurements, 18F-FDG uptake, and prognosis in patients with lung adenocarcinoma. J Nucl Med. 2004;45:1334–9.

    CAS  PubMed  Google Scholar 

  18. Akashi Y, Kuwabara Y, Ichiya Y, Sasaki M, Yoshida T, Fukumura T, et al. The partial volume effect correction for pulmonary mass lesions using a 68 Ga/68Ge transmission scan in PET study. Kaku Igaku. 1994;31:1511–7.

    CAS  PubMed  Google Scholar 

  19. Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med. 1991;324:1–8.

    Article  CAS  PubMed  Google Scholar 

  20. Yuan A, Yu CJ, Chen WJ, Lin FY, Kuo SH, Luh KT, et al. Correlation of total VEGF mRNA and protein expression with histologic type, tumour angiogenesis, patient survival and timing of relapse in non-small-cell lung cancer. Int J Cancer. 2000;89:475–83.

    Article  CAS  PubMed  Google Scholar 

  21. Cheung N, Wong MP, Yuen ST, Leung SY, Chung LP. Tissue-specific expression pattern of vascular endothelial growth factor isoforms in the malignant transformation of lung and colon. Hum Pathol. 1998;29:910–4.

    Article  CAS  PubMed  Google Scholar 

  22. Kondou M, Nagayasu T, Hidaka S, Tsuchiya T, Takeshita H, Yasutake T, et al. Correlation between angiogenesis and p53 expression in lung adenocarcinoma of young patients. Tohoku J Exp Med. 2009;217:101–7.

    Article  PubMed  Google Scholar 

  23. Stefanou D, Goussia AC, Arkoumani E, Agnantis NJ. Expression of vascular endothelial growth factor and the adhesion molecule E-cadherin in non-small cell lung cancer. Anticancer Res. 2003;23:4715–20.

    CAS  PubMed  Google Scholar 

  24. Pedersen MW, Holm S, Lund EL, Hojgaard L, Kristjansen PE. Coregulation of glucose uptake and vascular endothelial growth factor (VEGF) in two small-cell lung cancer (SCLC) sublines in vivo and in vitro. Neoplasia. 2001;3:80–7.

    Article  CAS  PubMed  Google Scholar 

  25. Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004;10:145–7.

    Article  CAS  PubMed  Google Scholar 

  26. Rodriguez-Porcel M, Cai W, Gheysens O, Willmann JK, Chen K, Wang H, et al. Imaging of VEGF receptor in a rat myocardial infarction model using PET. J Nucl Med. 2008;49:667–73.

    Article  PubMed  Google Scholar 

  27. Nagengast WB, de Vries EG, Hospers GA, Mulder NH, de Jong JR, Hollema H et al. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft. J Nucl Med. 2007;48:1313–9.

    Google Scholar 

  28. Nagengast WB, de Korte MA, Oude Munnink TH, Timmer-Bosscha H, den Dunnen WF, Hollema H, et al. 89Zr-bevacizumab PET of early antiangiogenic tumor response to treatment with HSP90 inhibitor NVP-AUY922. J Nucl Med. 2010;51:761–7.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a Grant for Project Research from High-Tech Research Center of Kanazawa Medical University (H2010-12, H2009-12, H2008-12, H2007-12, H2008-11, H2008-10, H2007-10, S2005-6, S2006-2), by The Policy Based Medical Services Network from the National Hospital Organization, and by a Grant-in Aid (19590370) for scientific research from the Ministry of Education, Japan.

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Correspondence to Kotaro Higashi.

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Guo, J., Higashi, K., Ueda, Y. et al. VEGF-A and its isoform VEGF121 mRNA expression measured by quantitative real-time RT-PCR: correlation with F-18 FDG uptake and aggressiveness of lung adenocarcinoma: preliminary study. Ann Nucl Med 25, 29–36 (2011). https://doi.org/10.1007/s12149-010-0427-1

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  • DOI: https://doi.org/10.1007/s12149-010-0427-1

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