Independent and Tissue-Specific Prognostic Impact of miR-126 in Nonsmall Cell Lung Cancer
AuthorDønnem, Tom; Lønvik, Kenneth; Eklo, Katrine; Berg, Thomas; Sørbye, Sveinung Wergeland; Al-Shibli, Khalid Ibrahim; Al-Saad, Samer; Andersen, Sigve; Stenvold, Helge; Bremnes, Roy M.; Busund, Lill-Tove
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.
PublisherJohn Wiley & Sons, Ltd.
CitationCancer 117(2011) nr. 14 s. 3193-3200
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