Open Access Research article

Stage and tissue-specific prognostic impact of miR-182 in NSCLC

Helge Stenvold12*, Tom Donnem12, Sigve Andersen12, Samer Al-Saad34, 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 Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway

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BMC Cancer 2014, 14:138  doi:10.1186/1471-2407-14-138

Published: 27 February 2014

Abstract

Background

MicroRNA (miR)-182 is frequently upregulated in cancers, has generally been viewed as an oncogene and is possibly connected to angiogenesis. We aimed to explore what impact miR-182 has in non-small cell lung cancer (NSCLC), and more explicitly its correlation with angiogenic markers.

Methods

From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarray blocks (TMAs). In situ hybridization (ISH) was used to detect the expression of miR-182 in tumor cells, and immunohistochemistry (IHC) was used to detect the expression of angiogenesis related protein markers.

Results

In univariate analyses, high tumor cell expression of miR-182 was a positive prognostic factor for patients with squamous cell carcinoma (SCC, P = 0.042) and stage II patients (P = 0.003). Also in the multivariate analysis, high tumor cell miR-182 expression was associated with a good prognosis in the same groups (SCC: HR 0.57, CI 95% 0.33-0.99, P = 0.048; stage II: HR 0.50, CI 95% 0.28-0.90, P = 0.020). We found significant correlations between miR-182 and the angiogenesis related markers FGF2, HIF2α and MMP-7.

Conclusion

In patients with SCC and in stage II patients, high tumor cell miR-182 expression is an independent positive prognostic factor.

Keywords:
NSCLC; Stage I-IIIA; Survival; Prognostic impact; miR-182; miRNA