Clin Exp Otorhinolaryngol.  2009 Dec;2(4):186-192. 10.3342/ceo.2009.2.4.186.

Expression of VEGF, HGF, IL-6, IL-8, MMP-9, Telomerase in Peripheral Blood of Patients with Head and Neck Squamous Cell Carcinoma

• Hong DY
• Lee BJ
• Lee JC
• Choi JS
• Wang SG
• Ro JH

• KMID: 1466496
• DOI: http://doi.org/10.3342/ceo.2009.2.4.186

Abstract

OBJECTIVES
This study investigated the telomerase expression in peripheral blood mononuclear cells (PBMCs) and the relationship between the serum level of several soluble factors such as vascular endothelial growth factor (VEGF), hepatocyte growth factor, interleukin (IL)-6, IL-8, and matrix metallopeptidase-9 and the clinicopathological features of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Peripheral blood samples were collected from 50 HNSCC patients and 15 normal controls. The telomerase activity in the PBMCs was measured by Telomere Repeat Amplification Protocols. The serum levels of the soluble factors were analyzed by enzyme-linked immunosorbent assay. RESULTS: The expression of telomerase in the PBMCs of HNSCC patients was significantly correlated with the N and American Joint Committee on Cancer (AJCC) stages. The serum VEGF level was significantly higher in the patients with an advanced T stage, N stage and AJCC stage. Serum VEGF was significantly related with the expression of telomerase in the PBMCs. The telomerase expression and the VEGF expression were shown to be independent factors associated with poor survival. CONCLUSION: The telomerase expression in the PBMCs and the serum VEGF level of HNSCC patients were significantly correlated with the N stage, the AJCC stage and the prognosis.

Keyword

Telomerase; Peripheral blood mononuclear cells; Vascular endothelial growth factors; Prognosis; Prognostic markers

MeSH Terms

Carcinoma, Squamous Cell
Enzyme-Linked Immunosorbent Assay
Head
Hepatocyte Growth Factor
Humans
Interleukin-6
Interleukin-8
Interleukins
Joints
Neck
Prognosis
Telomerase
Telomere
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Hepatocyte Growth Factor
Interleukin-6
Interleukin-8
Interleukins
Telomerase
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors

Figure

• 

  Fig. 1 Kaplan-Meier overall survival curves. There are significant differences in the Kaplan-Meier overall survival curves related to the telomerase expression and the serum vascular endothelial growth factor (VEGF) level. (A) Telomerase expression (P=0.045). (B) Serum VEGF level (P=0.028). (C) Serum hepatocyte growth factor level (P=0.172). (D) Serum interleukin (IL)-6 level (P=0.870). (E) Serum IL-8 level (P=0.675). (F) Serum matrix metalloproteinase-9 level (P=0.542).

Reference

1. Druzgal CH, Chen Z, Yeh NT, Thomas GR, Ondrey FG, Duffey DC, et al. A pilot study of longitudinal serum cytokine and angiogenesis factor levels as markers of therapeutic response and survival in patients with head and neck squamous cell carcinoma. Head Neck. 2005; 9. 27(9):771–784. PMID: 15920746.

2. Hathaway B, Landsittel DP, Gooding W, Whiteside TL, Grandis JR, Siegfried JM, et al. Multiplexed analysis of serum cytokines as biomarkers in squamous cell carcinoma of the head and neck patients. Laryngoscope. 2005; 3. 115(3):522–527. PMID: 15744170.

3. Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991; 1. 25. 64(2):327–336. PMID: 1703045.

4. Lee BJ, Wang SG, Choi JS, Lee JC, Goh EK, Kim MG. The prognostic value of telomerase expression in peripheral blood mononuclear cells of head and neck cancer patients. Am J Clin Oncol. 2006; 4. 29(2):163–167. PMID: 16601436.

5. Pries R, Wollenberg B. Cytokines in head and neck cancer. Cytokine Growth Factor Rev. 2006; 6. 17(3):141–146. PMID: 16540364.

6. Gokhale AS, Haddad RI, Cavacini LA, Wirth L, Weeks L, Hallar M, et al. Serum concentrations of interleukin-8, vascular endothelial growth factor, and epidermal growth factor receptor in patients with squamous cell cancer of the head and neck. Oral Oncol. 2005; 1. 41(1):70–76. PMID: 15598588.

7. Ruokolainen H, Paakko P, Turpeenniemi-Hujanen T. Serum matrix metalloproteinase-9 in head and neck squamous cell carcinoma is a prognostic marker. Int J Cancer. 2005; 9. 01. 116(3):422–427. PMID: 15818624.

8. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, et al. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994; 12. 266(5193):2011–2015. PMID: 7605428.

9. Ge P, Zhang B, Zhang J, Gao Z, He W. Telomerase activity of peripheral blood mononuclear cells from patients with laryngeal carcinoma. Am J Clin Oncol. 2004; 4. 27(2):191–194. PMID: 15057160.

10. Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB. Telomere end-replication problem and cell aging. J Mol Biol. 1992; 6. 225(4):951–960. PMID: 1613801.

11. Soria JC, Gauthier LR, Raymond E, Granotier C, Morat L, Armand JP, et al. Molecular detection of telomerase-positive circulating epithelial cells in metastatic breast cancer patients. Clin Cancer Res. 1999; 5. 5(5):971–975. PMID: 10353728.

12. Liao CT, Tung-Chieh Chang J, Wang HM, Chen IH, Lin CY, Chen TM, et al. Telomerase as an independent prognostic factor in head and neck squamous cell carcinoma. Head Neck. 2004; 6. 26(6):504–512. PMID: 15162351.

13. Taga S, Osaki T, Ohgami A, Imoto H, Yasumoto K. Prognostic impact of telomerase activity in non-small cell lung cancers. Ann Surg. 1999; 11. 230(5):715–720. PMID: 10561097.

14. Hiyama E, Hiyama K. Clinical utility of telomerase in cancer. Oncogene. 2002; 1. 21(4):643–649. PMID: 11850791.

15. Kumar H, Heer K, Lee PW, Duthie GS, MacDonald AW, Greenman J, et al. Preoperative serum vascular endothelial growth factor can predict stage in colorectal cancer. Clin Cancer Res. 1998; 5. 4(5):1279–1285. PMID: 9607588.

16. Teknos TN, Cox C, Yoo S, Chepeha DB, Wolf GT, Bradford CR, et al. Elevated serum vascular endothelial growth factor and decreased survival in advanced laryngeal carcinoma. Head Neck. 2002; 11. 24(11):1004–1011. PMID: 12410536.

17. Chiu CP, Harley CB. Replicative senescence and cell immortality: the role of telomeres and telomerase. Proc Soc Exp Biol Med. 1997; 2. 214(2):99–106. PMID: 9034126.

18. Zaccagnini G, Gaetano C, Della Pietra L, Nanni S, Grasselli A, Mangoni A, et al. Telomerase mediates vascular endothelial growth factor-dependent responsiveness in a rat model of hind-limb ischemia. J Biol Chem. 2005; 4. 280(15):14790–14798. PMID: 15687494.

19. Shao R, Guo X. Human microvascular endothelial cells immortalized with human telomerase catalytic protein: a model for the study of in vitro angiogenesis. Biochem Biophys Res Commun. 2004; 9. 321(4):788–794. PMID: 15358096.