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Serum Tumor Markers, Hypoxia-Inducible factor-1α HIF-1α and Vascular Endothelial Growth Factor, in Patients with Non-small Cell Lung Cancer Before and after Intervention

  • Liang, Jun (Department of Oncology, Wuxi People's Hospital of Huishan District) ;
  • Qian, Ying (Department of Oncology, Wuxi People's Hospital of Huishan District) ;
  • Xu, Dan (Department of Oncology, Wuxi People's Hospital of Huishan District) ;
  • Yin, Qun (Nursing Department, Wuxi People's Hospital of Huishan District) ;
  • Pan, Hui-Juan (Nursing Department, Wuxi People's Hospital of Huishan District)
  • Published : 2013.06.30

Abstract

Objective: To explore changes in the serum tumor makers, hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF) level and their relations in patients with non-small cell lung cancer (NSCLC) before and after intervention. Materials and Methods: Forty patients with NSCLC and 40 healthy individuals undergoing physical examination in our hospital provided the observation and control groups. HIF-$1{\alpha}$ and VEGF levels in serum were detected by enzyme-linked immuno-sorbent assay (ELISA) in the observation group before and after intervention and in control group on the day of physical examination, along with serum carcino-embryonic antigen (CEA), neuron-speci ic enolase (NSE) and squamous cell carcinoma antigen (SCC) levels in the observation group with a fully automatic biochemical analyzer. Clinical effects and improvement of life quality in the observation group were also evaluated. Results: The total effective rate and improvement of life quality after treatment in observation group were 30.0% and 32.5%, respectively. Serum HIF-$1{\alpha}$ and VEGF levels in the control group were lower than that in observation group (p<0.01), but remarkably elevatedafter intervention (p<0.01). In addition, serum CEA, NSE and SCC levels were apparently lowered by treatment (p<0.01). Serum HIF-$1{\alpha}$ demonstrated a positive relation with VEGF level (p<0.01) and was inversely related with CEA, NSE and SCC levels (p<0.01). Conclusions: Significant correlations exist between marked increase of serum HIF-$1{\alpha}$ and VEGF levels and decrease of indexes related to hematological tumor markers in NSCLC patients after intervention.

Keywords

References

  1. Andersen S, Donnem T, Stenvold H, et al (2011). Overexpression of the HIF hydroxylases PHD1, PHD2, PHD3 and FIH are individually and collectively unfavorable prognosticators for NSCLC survival. PLoS One, 6, e23847. https://doi.org/10.1371/journal.pone.0023847
  2. Choi YJ, Rho JK, Lee SJ, et al (2009). HIF-1alpha modulation by topoisomerase inhibitors in non-small cell lung cancer cell lines. J Cancer Res Clin Oncol, 135, 1047-53. https://doi.org/10.1007/s00432-009-0543-2
  3. Deacon K, Onion D, Kumari R, et al (2012). Elevated SP-1 transcription factor expression and activity drives basal and hypoxia-induced vascular endothelial growth factor (VEGF) expression in non-small cell lung cancer. J Biol Chem, 287, 39967-81. https://doi.org/10.1074/jbc.M112.397042
  4. Falchook GS, Naing A, Hong DS, et al (2013). Dual EGFR inhibition in combination with anti-VEGF treatment: a phase I clinical trial in non-small cell lung cancer. Oncotarget, 4, 118-27.
  5. Frechen D, Kr ger S, Cornelissen C, et al (2011). Interventional radiological therapies in lung oncology. Pneumologie, 65, 525-31. https://doi.org/10.1055/s-0030-1256503
  6. Furrukh M, Burney IA, Kumar S, et al (2013). Improving Outcomes in Advanced Lung Cancer: Maintenance therapy in non-small-cell lung carcinoma. Sultan Qaboos Univ Med J, 13, 3-18. https://doi.org/10.12816/0003190
  7. Jackson AL, Zhou B, Kim WY (2010). HIF, hypoxia and the role of angiogenesis in non-small cell lung cancer. Expert Opin Ther Targets, 14, 1047-57. https://doi.org/10.1517/14728222.2010.511617
  8. Jacoby JJ, Erez B, Korshunova MV, et al (2010). Treatment with HIF-1alpha antagonist PX-478 inhibits progression and spread of orthotopic human small cell lung cancer and lung adenocarcinoma in mice. J Thorac Oncol, 5, 940-9.
  9. Kausar H, Jeyabalan J, Aqil F, et al (2012). Berry anthocyanidins synergistically suppress growth and invasive potential of human non-small-cell lung cancer cells. Cancer Lett, 325, 54-62. https://doi.org/10.1016/j.canlet.2012.05.029
  10. Kim SJ, Rabbani ZN, Dewhirst MW, et al (2005). Expression of HIF-1alpha, CA IX, VEGF, and MMP-9 in surgically resected non-small cell lung cancer. Lung Cancer, 49, 325-35. https://doi.org/10.1016/j.lungcan.2005.03.036
  11. Lazarev SM, Massard Zh, Reshetov AV, et al (2010). Role of biological tumor markers CEA, Cyfra-21, NSE, TU M2-PK in diagnosis and treatment of lung cancer. Vestn Khir Im II Grek, 169, 39-43.
  12. Lee BE, Kletsman E, Rutledge JR, et al (2012). Utility of endobronchial ultrasound-guided mediastinal lymph node biopsy in patients with non-small cell lung cancer. J Thorac Cardiovasc Surg, 143, 585-90. https://doi.org/10.1016/j.jtcvs.2011.11.022
  13. Li CG, Huang XE, Xu L, Li Y, Lu YY (2012). Clinical application of serum tumor associated material (TAM) from non-small cell lung cancer patients. Asian Pac J Cancer Prev, 13, 301-4. https://doi.org/10.7314/APJCP.2012.13.1.301
  14. Li Y, Huang XE, Jin GF, Shen HB, Xu L (2011). Lack of any relationship between chemotherapy toxicity in non-small cell lung cancer cases and polymorphisms in XRCC1 codon 399 or XPD codon 751. Asian Pac J Cancer Prev, 12, 739-42.
  15. Liu YC, Zhou SB, Gao F, et al (2013). Chemotherapy and late course three dimensional conformal radiotherapy for treatment of patients with stage III non- small cell lung cancer. Asian Pac J Cancer Prev, 14, 2663-5. https://doi.org/10.7314/APJCP.2013.14.4.2663
  16. Lu YY, Huang XE, Xu L, et al (2013). Potential predictors of sensitivity to pemetrexed as first-line chemotherapy for patients with advanced non-squamous NSCLCs. Asian Pac J Cancer Prev, 14, 2005-8. https://doi.org/10.7314/APJCP.2013.14.3.2005
  17. Ma S, Shen L, Qian N, et al (2011-2012). The prognostic values of CA125, CA19.9, NSE, AND SCC for stage I NSCLC are limited. Cancer Biomark, 10, 155-62.
  18. Nakajima T, Anayama T, Koike T, et al (2012). Endobronchial ultrasound doppler image features correlate with mRNA expression of HIF1-_ and VEGF-C in patients with nonsmall-cell lung cancer. J Thorac Oncol, 7, 1661-7. https://doi.org/10.1097/JTO.0b013e318265b4df
  19. Pallis AG, Syrigos KN (2013). Targeting tumor neovasculature in non-small-cell lung cancer. Crit Rev Oncol Hematol, 86, 130-42. https://doi.org/10.1016/j.critrevonc.2012.10.003
  20. Ramlau R, Gorbunova V, Ciuleanu TE, et al (2012). Aflibercept and Docetaxel versus Docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. J Clin Oncol, 30, 3640-7. https://doi.org/10.1200/JCO.2012.42.6932
  21. Sandler A, Hirsh V, Reck M, et al (2012). An evidence-based review of the incidence of CNS bleeding with anti-VEGF therapy in non-small cell lung cancer patients with brain metastases. Lung Cancer, 78, 1-7. https://doi.org/10.1016/j.lungcan.2012.07.004
  22. Siejka A, Barabutis N, Schally AV (2012). GHRH antagonist inhibits focal adhesion kinase (FAK) and decreases expression of vascular endothelial growth factor (VEGF) in human lung cancer cells in vitro. Peptides, 37, 63-8. https://doi.org/10.1016/j.peptides.2012.07.010
  23. Singh-Gupta V, Joiner MC, Runyan L, et al (2011). Soy isoflavones augment radiation effect by inhibiting APE1/Ref-1 DNA repair activity in non-small cell lung cancer. J Thorac Oncol, 6, 688-98. https://doi.org/10.1097/JTO.0b013e31821034ae
  24. Tanabe T, Koizumi T, Tsushima K, et al (2010). Comparative study of three different catheters for CT imagingbronchoscopy-guided radiofrequency ablation as a potential and novel interventional therapy for lung cancer. Chest, 137, 890-7. https://doi.org/10.1378/chest.09-1065
  25. Wang Y, Huang L, Yang Y, et al (2013). Effects of autocrine vascular endothelial growth factor (VEGF) in non-small cell lung cancer cell line A549. Mol Biol Rep, 40, 3093-9. https://doi.org/10.1007/s11033-012-2383-4
  26. Wouters A, Pauwels B, Lambrechts HA, et al (2011). Retention of the in vitro radiosensitizing potential of gemcitabine under anoxic conditions, in p53 wild-type and p53-deficient non-small-cell lung carcinoma cells. Int J Radiat Oncol Biol Phys, 80, 558-66. https://doi.org/10.1016/j.ijrobp.2010.12.051
  27. Yan PW, Huang XE, Yan F, et al (2011). Influence of MDR1 gene codon 3435 polymorphisms on outcome of platinumbased chemotherapy for advanced non small cell lung cancer. Asian Pac J Cancer Prev, 12, 2291-4.

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