Open Access Open Badges Research article

High tumor cell expression of microRNA-21 in node positive non-small cell lung cancer predicts a favorable clinical outcome

Helge Stenvold12*, Tom Donnem12, Sigve Andersen12, Samer Al-Saad34, Andrej Valkov34, Mona Irene Pedersen14, Lill-Tove Busund34 and Roy M Bremnes12

Author Affiliations

1 Institute of Clinical Medicine, University of Tromso, Tromso, Norway

2 Department of Oncology, University Hospital of North Norway, Tromso 9038, Norway

3 Institute of Medical Biology, University of Tromso, Tromso, Norway

4 Dept of Clinical Pathology, University Hospital of North Norway, Tromso, Norway

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BMC Clinical Pathology 2014, 14:9  doi:10.1186/1472-6890-14-9

Published: 13 February 2014



MicroRNA (miR)-21 has been revealed as an oncogene in cancer development, and is one of the miRNAs closely connected to angiogenesis. We aimed to explore the impact of miR-21 expression in both tumor and stromal compartments of non-small cell lung cancer (NSCLC), and correlations between miR-21 and angiogenic protein markers.


From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarrays (TMAs). In situ hybridization (ISH) was used to detect the expression of miR-21 separately in tumor cells and stromal cells of the tumor, and immunohistochemistry (IHC) was used to detect the expression of the protein markers protein kinase B (Akt), phosphatidylinositol-3-kinase (PI3K), hypoxia induced factor 1 (HIF1α) and vascular endothelial growth factor-A (VEGF-A).


In univariate analyses, high tumor cell expression of miR-21 in patients with lymph node metastasis was a positive prognostic factor (P = 0.024). High stromal miR-21 expression had a negative prognostic impact (P = 0.022). In the multivariate analysis, low tumor mir-21 expression in node positive patients was an independent adverse prognostic factor (HR 2.03, CI 95% 1.09-3.78, P = 0.027).


In patients with lymph node metastasis, miR-21 expression in tumor cells is an independent positive prognostic factor. High stromal miR-21 expression is a negative prognostic factor.

NSCLC; Stage I-IIIA; Survival; Prognostic impact; miR-21; miRNA