Higher serum nitrate levels are associated with poor survival in lung cancer patients

被引:18
作者
Colakogullari, Mukaddes
Ulukaya, Engin [1 ]
Yilmaztepe, Arzu
Ocakoglu, Gokhan
Yilmaz, Meryem
Karadag, Mehmet
Tokullugil, Asuman
机构
[1] Uludag Univ Tip Fak, Dept Biochem, TR-16059 Gorukle, Turkey
[2] Uludag Univ, Fac Med, Dept Biostat, Gorukle, Turkey
[3] Uludag Univ, Fac Med, Dept Chest Dis & TB, Gorukle, Turkey
关键词
nitric oxide (NO); vascular endothelial growth factor-A (VEGF-A); lung cancer; survival; serum nitrite/nitrate;
D O I
10.1016/j.clinbiochem.2006.06.008
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Objectives: Angiogenic factors induce tumour growth and angiogenesis which leads to tumour metastasis and a poor survival rate. This study aimed to assess the possible roles of nitric oxide (NO) and vascular endothelial growth factor-A (VEGF-A) in the overall survival of patients with late stage lung cancer. Design and methods: The study was carried out with primary lung carcinoma patients (n = 31) and healthy controls (n = 15). Pre- and post-cisplatin-based chemotherapy serum nitrite/nitrate levels were measured as nitrite after enzymatic conversion followed by Griess reaction and serum VEGF-A analysis was performed using ELISA. After patient follow-up, survival rates were calculated by using the Kaplan-Meier method [Dudek et al. Cancer Invest 2005; 23(3):193-200]. Results: The serum nitrite/nitrate and VEGF-A levels of lung cancer patients and the control group were 93.7 +/- 48.9 and 63.7 +/- 32.2 PM (p=0.018), and 620 +/- 491 and 255 +/- 157 pg/mL (p = 0.001), respectively, High nitrite/nitrate (> 67.2 mu M) concentration had statistically significant effects on overall survival (Cox analysis, p = 0.026). The overall survival of the lung cancer patients with higher serum nitrate concentrations was significantly less than the ones with lower serum nitrite/nitrate (Kaplan-Meier survival functions test, log rank significance = 0.0007). Conclusion: Our results suggest that having a high serum nitrite/nitrate concentration is a strong indicator of poor survival for late stage lung cancer patients. However, this conclusion deserves to be elucidated further by using a larger sample size. (c) 2006 The Canadian Society of Clinical Chemists. All rights reserved.
引用
收藏
页码:898 / 903
页数:6
相关论文
共 39 条
[1]   Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53 [J].
Ambs, S ;
Bennett, WP ;
Merriam, WG ;
Ogunfusika, MO ;
Oser, SM ;
Khan, MA ;
Jones, RT ;
Harris, CC .
BRITISH JOURNAL OF CANCER, 1998, 78 (02) :233-239
[2]   Vascular endothelial growth factor in the serum of patients with non-small cell lung cancer: correlation with platelet and leukocyte counts [J].
Choi, JH ;
Kim, HC ;
Lim, HY ;
Nam, DK ;
Kim, HS ;
Yi, JW ;
Chun, M ;
Oh, YT ;
Kang, S ;
Park, KJ ;
Hwang, SC ;
Lee, YH ;
Hahn, MH .
LUNG CANCER, 2001, 33 (2-3) :171-179
[3]   Circulating angiogenic cytokines in patients with advanced non-small cell lung cancer: Correlation with treatment response and survival [J].
Dudek, AZ ;
Mahaseth, H .
CANCER INVESTIGATION, 2005, 23 (03) :193-200
[4]   Tumor cell nitric oxide inhibits cell growth in vitro, but stimulates tumorigenesis and experimental lung metastasis in vivo [J].
Edwards, P ;
Cendan, JC ;
Topping, DB ;
Moldawer, LL ;
MacKay, S ;
Copeland, EM ;
Lind, DS .
JOURNAL OF SURGICAL RESEARCH, 1996, 63 (01) :49-52
[5]   Significant correlation of nitric oxide synthase activity and p53 gene mutation in stage I lung adenocarcinoma [J].
Fujimoto, H ;
Sasaki, J ;
Matsumoto, M ;
Suga, M ;
Ando, Y ;
Iggo, R ;
Tada, M ;
Saya, H ;
Ando, M .
JAPANESE JOURNAL OF CANCER RESEARCH, 1998, 89 (07) :696-702
[6]   Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability [J].
Fukumura, D ;
Gohongi, T ;
Kadambi, A ;
Izumi, Y ;
Ang, J ;
Yun, CO ;
Buerk, DG ;
Huang, PL ;
Jain, RK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) :2604-2609
[7]   Tumour-derived and host-derived nitric oxide differentially regulate breast carcinoma metastasis to the lungs [J].
Gauthier, N ;
Lohm, S ;
Touzery, C ;
Chantôme, A ;
Perette, B ;
Reveneau, S ;
Brunotte, F ;
Juillerat-Jeanneret, L ;
Jeannin, JF .
CARCINOGENESIS, 2004, 25 (09) :1559-1565
[8]   Apoptosis as a measure of chemosensitivity to cisplatin and taxol therapy in ovarian cancer cell lines [J].
Gibb, RK ;
Taylor, DD ;
Wan, T ;
OConnor, DM ;
Doering, DL ;
GercelTaylor, C .
GYNECOLOGIC ONCOLOGY, 1997, 65 (01) :13-22
[9]   ANALYSIS OF NITRATE, NITRITE, AND [N-15]-LABELED NITRATE IN BIOLOGICAL-FLUIDS [J].
GREEN, LC ;
WAGNER, DA ;
GLOGOWSKI, J ;
SKIPPER, PL ;
WISHNOK, JS ;
TANNENBAUM, SR .
ANALYTICAL BIOCHEMISTRY, 1982, 126 (01) :131-138
[10]  
Herr I, 2003, CANCER RES, V63, P3112