The first 2 authors contributed equally to this work.
Independent and tissue-specific prognostic impact of miR-126 in nonsmall cell lung cancer
Coexpression with vascular endothelial growth factor-A predicts poor survival
Article first published online: 24 JAN 2011
Copyright © 2011 American Cancer Society
Volume 117, Issue 14, pages 3193–3200, 15 July 2011
How to Cite
Donnem, T., Lonvik, K., Eklo, K., Berg, T., Sorbye, S. W., Al-Shibli, K., Al-Saad, S., Andersen, S., Stenvold, H., Bremnes, R. M. and Busund, L.-T. (2011), Independent and tissue-specific prognostic impact of miR-126 in nonsmall cell lung cancer. Cancer, 117: 3193–3200. doi: 10.1002/cncr.25907
- Issue published online: 30 JUN 2011
- Article first published online: 24 JAN 2011
- Manuscript Accepted: 3 DEC 2010
- Manuscript Revised: 22 NOV 2010
- Manuscript Received: 20 SEP 2010
Angiogenesis is pivotal in tumor development. Vascular endothelial growth factor-A (VEGF-A) is considered one of the most important angiogenic factors, but lately several microRNAs (miRs) have been associated with vascular development. miR-126 has been related to tumor angiogenesis and in the regulation of VEGF-A. The authors aimed to investigate the prognostic impact of miR-126 and its co-expression with VEGF-A in nonsmall cell lung cancer (NSCLC) patients.
Tumor tissue samples from 335 resected stage I to IIIA NSCLC patients were obtained and tissue microarrays (TMAs) were constructed with 4 cores from each tumor specimen. VEGF-A expression was evaluated by immunohistochemistry, and in situ hybridization was used to evaluate the expression of miR-126.
In the total material, miR-126 was a significant negative prognostic factor in both univariate (P = .005) and multivariate analyses (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.2-2.8, P = .01). Stratified by histology, miR-126 was only significant in squamous cell carcinomas (univariate: P < .001; multivariate: HR 3.1, CI 95% 1.7-5.6, P<.001). Stratified by lymph node status, miR-126 was significant only in the lymph node-positive subgroup (univariate: P<.001; multivariate: HR 4.1, CI 95% 2.0-8.4, P < .001). High miR-126 expression correlated significantly with high VEGF-A expression (P = .037). The co-expression of miR-126 and VEGF-A had a significant prognostic impact (P = .002), with 5-year survival rates of 68%, 51%, and 42% for low/low (n = 150), mixed combinations (n = 129), and high/high (n = 35) expression, respectively.
miR-126 is a strong and independent negative prognostic factor in NSCLC, and its prognostic impact appears related primarily to histology and nodal status. Cancer 2011. © 2011 American Cancer Society.